TY  - JOUR
AU  - Šuljagić, Vesna
AU  - Đurić-Petković, Danijela
AU  - Lazić, Srdan
AU  - Mladenović, Jovan
AU  - Rakonjac, Bojan
AU  - Opačić, Dolores
AU  - Ljubenović, Nenad
AU  - Milojković, Biljana
AU  - Radojević, Katarina
AU  - Nenezić, Ivana
AU  - Rančić, Nemanja
PY  - 2023
UR  - http://intor.torlakinstitut.com/handle/123456789/655
AB  - Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resulting coronavirus disease 2019 (COVID-19) has caused a fast-moving pandemic. Diagnostic testing, aimed to identify patients infected with SARS-CoV-2, plays a key role in controlling the COVID-19 pandemic in different populations. (2) Methods: This retrospective cohort study aimed to investigate predictors associated with positive polymerase chain reaction (PCR) SARS-CoV-2 test results in hospitalized patients, healthcare workers (HCWs), and military personnel (MP) during 2020, before the widespread availability of COVID-19 vaccines. Persons with a positive test result were compared with persons with a negative test result in three cohorts during the study period. (3) Results: A total of 6912 respondents were tested, and 1334 (19.3%) of them had positive PCR SARS-CoV-2 test results. Contact with a known COVID-19 case within 14 days (p < 0.001; OR: 1.48; 95% CI: 1.25–1.76), fever (p < 0.001; OR: 3.66; 95% CI: 3.04–4.41), cough (p < 0.001; OR: 1.91; 95% CI: 1.59–2.30), headache (p = 0.028; OR: 1.24; 95% CI: 1.02–1.50), and myalgia/arthralgia (p < 0.001; OR: 1.99; 95% CI: 1.65–2.42) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of MP. Furthermore, fever (p < 0.001; OR: 2.75; 95% CI: 1.83–4.13), cough (p < 0.001; OR: 2.04; 95% CI: 1.32–3.13), headache (p = 0.008; OR: 1.76; 95% CI: 1.15–2.68), and myalgia/arthralgia (p = 0.039; OR: 1.58; 95% CI: 1.02–2.45) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of HCWs. Moreover, independent predictors of positive PCR SARS-CoV-2 test results in hospitalized patients were contact with a known COVID-19 case within 14 days (p < 0.001; OR: 2.56; 95% CI: 1.71–3.83), fever (p < 0.001; OR: 1.89; 95% CI: 1.38–2.59), pneumonia (p = 0.041; OR: 1.45; 95% CI: 1.01–2.09), and neurological diseases (p = 0.009; OR: 0.375; 95% CI: 0.18–0.78). (4) Conclusions: According to data gathered from cohorts of hospitalized patients, HCWs, and MP, before the widespread availability of COVID-19 vaccines in Serbia, we can conclude that predictors of positive PCR SARS-CoV-2 test results in MP and HCWs were similar. Accurate estimates of COVID-19 in different population groups are important for health authorities.
PB  - MDPI
T2  - International Journal of Environmental Research and Public Health
T1  - Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020
IS  - 4
SP  - 3601
VL  - 20
DO  - 10.3390/ijerph20043601
ER  - 

@article{
author = "Šuljagić, Vesna and Đurić-Petković, Danijela and Lazić, Srdan and Mladenović, Jovan and Rakonjac, Bojan and Opačić, Dolores and Ljubenović, Nenad and Milojković, Biljana and Radojević, Katarina and Nenezić, Ivana and Rančić, Nemanja",
year = "2023",
abstract = "Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its resulting coronavirus disease 2019 (COVID-19) has caused a fast-moving pandemic. Diagnostic testing, aimed to identify patients infected with SARS-CoV-2, plays a key role in controlling the COVID-19 pandemic in different populations. (2) Methods: This retrospective cohort study aimed to investigate predictors associated with positive polymerase chain reaction (PCR) SARS-CoV-2 test results in hospitalized patients, healthcare workers (HCWs), and military personnel (MP) during 2020, before the widespread availability of COVID-19 vaccines. Persons with a positive test result were compared with persons with a negative test result in three cohorts during the study period. (3) Results: A total of 6912 respondents were tested, and 1334 (19.3%) of them had positive PCR SARS-CoV-2 test results. Contact with a known COVID-19 case within 14 days (p < 0.001; OR: 1.48; 95% CI: 1.25–1.76), fever (p < 0.001; OR: 3.66; 95% CI: 3.04–4.41), cough (p < 0.001; OR: 1.91; 95% CI: 1.59–2.30), headache (p = 0.028; OR: 1.24; 95% CI: 1.02–1.50), and myalgia/arthralgia (p < 0.001; OR: 1.99; 95% CI: 1.65–2.42) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of MP. Furthermore, fever (p < 0.001; OR: 2.75; 95% CI: 1.83–4.13), cough (p < 0.001; OR: 2.04; 95% CI: 1.32–3.13), headache (p = 0.008; OR: 1.76; 95% CI: 1.15–2.68), and myalgia/arthralgia (p = 0.039; OR: 1.58; 95% CI: 1.02–2.45) were independently associated with positive PCR SARS-CoV-2 test results in the cohort of HCWs. Moreover, independent predictors of positive PCR SARS-CoV-2 test results in hospitalized patients were contact with a known COVID-19 case within 14 days (p < 0.001; OR: 2.56; 95% CI: 1.71–3.83), fever (p < 0.001; OR: 1.89; 95% CI: 1.38–2.59), pneumonia (p = 0.041; OR: 1.45; 95% CI: 1.01–2.09), and neurological diseases (p = 0.009; OR: 0.375; 95% CI: 0.18–0.78). (4) Conclusions: According to data gathered from cohorts of hospitalized patients, HCWs, and MP, before the widespread availability of COVID-19 vaccines in Serbia, we can conclude that predictors of positive PCR SARS-CoV-2 test results in MP and HCWs were similar. Accurate estimates of COVID-19 in different population groups are important for health authorities.",
publisher = "MDPI",
journal = "International Journal of Environmental Research and Public Health",
title = "Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020",
number = "4",
pages = "3601",
volume = "20",
doi = "10.3390/ijerph20043601"
}

Šuljagić, V., Đurić-Petković, D., Lazić, S., Mladenović, J., Rakonjac, B., Opačić, D., Ljubenović, N., Milojković, B., Radojević, K., Nenezić, I.,& Rančić, N.. (2023). Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020. in International Journal of Environmental Research and Public Health
MDPI., 20(4), 3601.
https://doi.org/10.3390/ijerph20043601

Šuljagić V, Đurić-Petković D, Lazić S, Mladenović J, Rakonjac B, Opačić D, Ljubenović N, Milojković B, Radojević K, Nenezić I, Rančić N. Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020. in International Journal of Environmental Research and Public Health. 2023;20(4):3601.
doi:10.3390/ijerph20043601 .

Šuljagić, Vesna, Đurić-Petković, Danijela, Lazić, Srdan, Mladenović, Jovan, Rakonjac, Bojan, Opačić, Dolores, Ljubenović, Nenad, Milojković, Biljana, Radojević, Katarina, Nenezić, Ivana, Rančić, Nemanja, "Epidemiological Predictors of Positive SARS-CoV-2 Polymerase Chain Reaction Test in Three Cohorts: Hospitalized Patients, Healthcare Workers, and Military Population, Serbia, 2020" in International Journal of Environmental Research and Public Health, 20, no. 4 (2023):3601,
https://doi.org/10.3390/ijerph20043601 . .

TY  - JOUR
AU  - Petrović, Raisa
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Živković, Irena
AU  - Minić, Rajna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/501
AB  - Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Life Sciences
T1  - Mouse strain and sex as determinants of immune response to trivalent influenza vaccine
EP  - 126
SP  - 117
VL  - 207
DO  - 10.1016/j.lfs.2018.05.056
ER  - 

@article{
author = "Petrović, Raisa and Bufan, Biljana and Arsenović-Ranin, Nevena and Živković, Irena and Minić, Rajna and Radojević, Katarina and Leposavić, Gordana",
year = "2018",
abstract = "Aims: The study examined the influence of sex and mouse strain on germinal center (GC) reaction and antibody responses to seasonal split trivalent influenza vaccine (TIV). Main methods: C57BL/6 and BALB/c mice of both sexes were immunized with TIV and examined for specific antibody response by ELISA. Splenic T follicular regulatory (Tfr), T follicular helper (Tfh) and GC B cells are detected by flow cytometry. The proliferative response of splenocytes, and concentrations of IFN-gamma and IL-4 upon restimulation with vaccine antigens were examined by 7-AAD staining and ELISA, respectively. Key findings: BALB/c mice developed more robust IgG responses to vaccine type A antigens than their sexmatched C57BL/6 counterparts, while that to B antigen did not differ between strains. In both strains IgG responses against type A vaccine antigens were greater in females than in males. The greater IgG responses correlated with lower splenic Tfr/Tfh and Tfr/GC B cell ratios and greater vaccine antigen-specific proliferative responses of CD4+ and B cells in splenocyte cultures. In both mouse strains IgG2a(c)/IgG1 ratios were comparable between sexes, but lower in BALB/c than in C57BL/6 mice indicating a shift in Th1/Th2 balance towards Th2 response in BALB/c ones. Consistently, splenocytes from BALB/c mice produced more IL-4 and less IFN-gamma than those from C57BL/6 mice. Significance: The study indicated that magnitude of humoral response to influenza type A haemagglutinins depends on mouse strain and sex, and thereby set background for the vaccination strategies taking into account biological sex, and in a longterm perspective individual differences in immune reactivity.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Life Sciences",
title = "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine",
pages = "126-117",
volume = "207",
doi = "10.1016/j.lfs.2018.05.056"
}

Petrović, R., Bufan, B., Arsenović-Ranin, N., Živković, I., Minić, R., Radojević, K.,& Leposavić, G.. (2018). Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences
Pergamon-Elsevier Science Ltd, Oxford., 207, 117-126.
https://doi.org/10.1016/j.lfs.2018.05.056

Petrović R, Bufan B, Arsenović-Ranin N, Živković I, Minić R, Radojević K, Leposavić G. Mouse strain and sex as determinants of immune response to trivalent influenza vaccine. in Life Sciences. 2018;207:117-126.
doi:10.1016/j.lfs.2018.05.056 .

Petrović, Raisa, Bufan, Biljana, Arsenović-Ranin, Nevena, Živković, Irena, Minić, Rajna, Radojević, Katarina, Leposavić, Gordana, "Mouse strain and sex as determinants of immune response to trivalent influenza vaccine" in Life Sciences, 207 (2018):117-126,
https://doi.org/10.1016/j.lfs.2018.05.056 . .

TY  - JOUR
AU  - Radojević, Katarina
AU  - Rakin, Ana
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Đikić, Jasmina
AU  - Bufan, Biljana
AU  - Vujnović, Ivana
AU  - Leposavić, Gordana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/409
AB  - The present study, through quantification of tyrosine hydroxylase (TH) expression and catecholamine (CA) content in the presence and in the absence of alpha-methyl-p-tyrosine (AMPT), a TH inhibitor, in adult thymic organ (ATOC) and thymocyte culture, demonstrated that thymic cells produce CAs. In addition, in ATOC an increase in beta(2)-adrenoceptor (AR) mRNA expression and beta(2)-AR thymocyte surface density was registered. Furthermore, AMPT (10(-4) M), as propranolol (10(-4) M), augmented thymocyte apoptosis and diminished thymocyte proliferation in ATOC. Propranolol exerted these effects acting on CD3(high) thymocytes. However, in thymocyte cultures, propranolol (10(-6) M) acting on the same-thymocyte subset exerted the opposing effect on thymocyte apoptosis and ConA-stimulated proliferation. This suggested that, depending on thymocyte microenvironment, differential effects can be induced through the same type of AR. Additionally, arterenol (10(-8) to 10(-6) M), similar to propranolol, diminished apoptosis, but increased ConA-stimulated thymocyte proliferation in thymocyte culture. However, differently from propranolol, arterenol affected manly CD3- thymocyte subset, which harbors majority of alpha(1)-AR+ thymocytes. Additionally, arterenol showed a dose-dependent decrease in efficiency of thymocyte apoptosis and proliferation modulation with the rise in its concentration. Considering greater affinity of arterenol for alpha(1)-ARs than for beta(2)-ARs, the previous findings could be attributable to increased engagement of beta(2)-ARs with the rise of arterenol concentration. Consistently, in the presence of propranolol (10(-6) M), a beta-AR blacker, the arterenol (10(-8) M) effects on thymocytes were augmented. In conclusion, thymic endogenous CAs, acting through distinct AR types and, possible, the same AR type (but in different cell microenvironment) may exert the opposing effects on thymocyte apoptosis/proliferation. (C) 2014 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment
EP  - 28
IS  - 1-2
SP  - 16
VL  - 272
DO  - 10.1016/j.jneuroim.2014.04.010
ER  - 

@article{
author = "Radojević, Katarina and Rakin, Ana and Pilipović, Ivan and Kosec, Duško and Đikić, Jasmina and Bufan, Biljana and Vujnović, Ivana and Leposavić, Gordana",
year = "2014",
abstract = "The present study, through quantification of tyrosine hydroxylase (TH) expression and catecholamine (CA) content in the presence and in the absence of alpha-methyl-p-tyrosine (AMPT), a TH inhibitor, in adult thymic organ (ATOC) and thymocyte culture, demonstrated that thymic cells produce CAs. In addition, in ATOC an increase in beta(2)-adrenoceptor (AR) mRNA expression and beta(2)-AR thymocyte surface density was registered. Furthermore, AMPT (10(-4) M), as propranolol (10(-4) M), augmented thymocyte apoptosis and diminished thymocyte proliferation in ATOC. Propranolol exerted these effects acting on CD3(high) thymocytes. However, in thymocyte cultures, propranolol (10(-6) M) acting on the same-thymocyte subset exerted the opposing effect on thymocyte apoptosis and ConA-stimulated proliferation. This suggested that, depending on thymocyte microenvironment, differential effects can be induced through the same type of AR. Additionally, arterenol (10(-8) to 10(-6) M), similar to propranolol, diminished apoptosis, but increased ConA-stimulated thymocyte proliferation in thymocyte culture. However, differently from propranolol, arterenol affected manly CD3- thymocyte subset, which harbors majority of alpha(1)-AR+ thymocytes. Additionally, arterenol showed a dose-dependent decrease in efficiency of thymocyte apoptosis and proliferation modulation with the rise in its concentration. Considering greater affinity of arterenol for alpha(1)-ARs than for beta(2)-ARs, the previous findings could be attributable to increased engagement of beta(2)-ARs with the rise of arterenol concentration. Consistently, in the presence of propranolol (10(-6) M), a beta-AR blacker, the arterenol (10(-8) M) effects on thymocytes were augmented. In conclusion, thymic endogenous CAs, acting through distinct AR types and, possible, the same AR type (but in different cell microenvironment) may exert the opposing effects on thymocyte apoptosis/proliferation. (C) 2014 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment",
pages = "28-16",
number = "1-2",
volume = "272",
doi = "10.1016/j.jneuroim.2014.04.010"
}

Radojević, K., Rakin, A., Pilipović, I., Kosec, D., Đikić, J., Bufan, B., Vujnović, I.,& Leposavić, G.. (2014). Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment. in Journal of Neuroimmunology
Elsevier, Amsterdam., 272(1-2), 16-28.
https://doi.org/10.1016/j.jneuroim.2014.04.010

Radojević K, Rakin A, Pilipović I, Kosec D, Đikić J, Bufan B, Vujnović I, Leposavić G. Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment. in Journal of Neuroimmunology. 2014;272(1-2):16-28.
doi:10.1016/j.jneuroim.2014.04.010 .

Radojević, Katarina, Rakin, Ana, Pilipović, Ivan, Kosec, Duško, Đikić, Jasmina, Bufan, Biljana, Vujnović, Ivana, Leposavić, Gordana, "Effects of catecholamines on thymocyte apoptosis and proliferation depend on thymocyte microenvironment" in Journal of Neuroimmunology, 272, no. 1-2 (2014):16-28,
https://doi.org/10.1016/j.jneuroim.2014.04.010 . .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Radojević, Katarina
AU  - Nacka-Aleksić, Mirjana
AU  - Leposavić, Gordana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/418
AB  - Objective: Considering a causal role of androgens in thymic involution, age-related remodeling of peripheral T-cell compartments in the absence of testicular hormones was evaluated. Methods: Rats were orchidectomized (ORX) at the age of 1 month, and T-peripheral blood lymphocytes (PBLs) and splenocytes from young (75-day-old) and aged (24-month-old) rats were examined for differentiation/activation and immunoregulatory marker expression. Results: In ORX rats, following the initial rise, the counts of CD4+ and CD8+ PBLs diminished with aging. This reflected the decline in thymic export as shown by recent thymic emigrant (RTE) enumeration. Orchidectomy increased the count of both of the major T-splenocyte subsets in young rats, and they (differently from controls) remained stable with aging. The CD4+:CD8+ T-splenocyte ratio in ORX rats shifted towards CD4+ cells compared to age-matched controls. Although in the major T-cell subsets in the blood and spleen from aged ORX rats the numbers of RTEs were comparable to the corresponding values in age-matched controls, the numbers of mature naive and memory/activated cells substantially differed. Compared with age-matched controls, in aged ORX rats the numbers of CD4+ mature naive PBLs and splenocytes were reduced, whereas those of CD4+ memory/activated cells (predictive of early mortality) were increased. Additionally, in spleens from aged ORX rats, despite unaltered thymic export, CD4+CD25+FoxP3+ and natural killer T cell counts were greater than in age-matched controls. Conclusion: (i) Age-related decline in thymopoietic efficacy is not dependent on androgen presence, and (ii) androgens are involved in the maintenance of peripheral T-cell (particularly CD4+ cell) homeostasis during aging. (C) 2014 S. Karger AG, Basel
PB  - Karger, Basel
T2  - Neuroimmunomodulation
T1  - Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way
EP  - 182
IS  - 4
SP  - 161
VL  - 21
DO  - 10.1159/000355349
ER  - 

@article{
author = "Arsenović-Ranin, Nevena and Kosec, Duško and Pilipović, Ivan and Bufan, Biljana and Stojić-Vukanić, Zorica and Radojević, Katarina and Nacka-Aleksić, Mirjana and Leposavić, Gordana",
year = "2014",
abstract = "Objective: Considering a causal role of androgens in thymic involution, age-related remodeling of peripheral T-cell compartments in the absence of testicular hormones was evaluated. Methods: Rats were orchidectomized (ORX) at the age of 1 month, and T-peripheral blood lymphocytes (PBLs) and splenocytes from young (75-day-old) and aged (24-month-old) rats were examined for differentiation/activation and immunoregulatory marker expression. Results: In ORX rats, following the initial rise, the counts of CD4+ and CD8+ PBLs diminished with aging. This reflected the decline in thymic export as shown by recent thymic emigrant (RTE) enumeration. Orchidectomy increased the count of both of the major T-splenocyte subsets in young rats, and they (differently from controls) remained stable with aging. The CD4+:CD8+ T-splenocyte ratio in ORX rats shifted towards CD4+ cells compared to age-matched controls. Although in the major T-cell subsets in the blood and spleen from aged ORX rats the numbers of RTEs were comparable to the corresponding values in age-matched controls, the numbers of mature naive and memory/activated cells substantially differed. Compared with age-matched controls, in aged ORX rats the numbers of CD4+ mature naive PBLs and splenocytes were reduced, whereas those of CD4+ memory/activated cells (predictive of early mortality) were increased. Additionally, in spleens from aged ORX rats, despite unaltered thymic export, CD4+CD25+FoxP3+ and natural killer T cell counts were greater than in age-matched controls. Conclusion: (i) Age-related decline in thymopoietic efficacy is not dependent on androgen presence, and (ii) androgens are involved in the maintenance of peripheral T-cell (particularly CD4+ cell) homeostasis during aging. (C) 2014 S. Karger AG, Basel",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way",
pages = "182-161",
number = "4",
volume = "21",
doi = "10.1159/000355349"
}

Arsenović-Ranin, N., Kosec, D., Pilipović, I., Bufan, B., Stojić-Vukanić, Z., Radojević, K., Nacka-Aleksić, M.,& Leposavić, G.. (2014). Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way. in Neuroimmunomodulation
Karger, Basel., 21(4), 161-182.
https://doi.org/10.1159/000355349

Arsenović-Ranin N, Kosec D, Pilipović I, Bufan B, Stojić-Vukanić Z, Radojević K, Nacka-Aleksić M, Leposavić G. Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way. in Neuroimmunomodulation. 2014;21(4):161-182.
doi:10.1159/000355349 .

Arsenović-Ranin, Nevena, Kosec, Duško, Pilipović, Ivan, Bufan, Biljana, Stojić-Vukanić, Zorica, Radojević, Katarina, Nacka-Aleksić, Mirjana, Leposavić, Gordana, "Androgens Contribute to Age-Associated Changes in Peripheral T-Cell Homeostasis Acting in a Thymus-Independent Way" in Neuroimmunomodulation, 21, no. 4 (2014):161-182,
https://doi.org/10.1159/000355349 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Perišić-Nanut, Milica
AU  - Stojić-Vukanić, Zorica
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/385
AB  - The study was undertaken considering that: i) androgens affect beta(2)-adrenoceptor (AR)-mediated catecholamine (CA) action in many tissues; and ii) peripubertal changes in both circulating androgen and thymic CA levels are implicated in rat thymic involution. Its aims were to: i) explore putative effects of the late prepubertal orchidectomy on thymic CA:beta(2)-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:beta(2)-AR complex from those elicited secondarily through altered influence of this complex components on each other's availability. Upon showing that prepubertal orchidectomy augmented the efficacy of thymopoiesis through increasing the thymocyte surface density of Thy-1, whose expression is negatively regulated by beta(2)-AR-mediated signaling, we examined the effects of orchidectomy and 14-day-long propranolol (PROP) treatment in orchidectomized (ORX) and sham-ORX rats on thymic norepinephrine (NE) concentration and metabolism and beta(2)-AR expression. Orchidectomy, despite an increase in the average NE amount per thymocyte and total thymocyte NE content diminished thymic NE concentration. This decrease reflected the diminished density of CA-synthesizing nerve fibers, CD68 + macrophages, cortical (aminopeptidase A+), and medullary (UEA-1+) thymic epithelial cells (TECs) and their CA content (probably due to lessened TH expression accompanied by increased MAO-A expression). Moreover, orchidectomy decreased the surface beta(2)-AR expression on thymocytes, CD68+ macrophages and OX-62+ dendritic cells, but increased its expression on the TECs. In sham-ORX rats, PROP reduced thymic NE concentration by diminishing TH expression in the thymic cells. Additionally, PROP in thymocytes and thymic stromal cells diminished and enhanced the beta(2)-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):beta(2)-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to beta-AR blockade by altering thymic NE and beta(2)-AR availability. Collectively, the results showed that testicular hormones contribute to alterations in thymus/thymopoiesis during the critical peripubertal period by shaping modulatory sympathetic influence and CA autocrine/paracrine action within the organ. (C) 2013 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis
EP  - 35
IS  - 1-2
SP  - 20
VL  - 265
DO  - 10.1016/j.jneuroim.2013.09.021
ER  - 

@article{
author = "Pilipović, Ivan and Radojević, Katarina and Kosec, Duško and Perišić-Nanut, Milica and Stojić-Vukanić, Zorica and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2013",
abstract = "The study was undertaken considering that: i) androgens affect beta(2)-adrenoceptor (AR)-mediated catecholamine (CA) action in many tissues; and ii) peripubertal changes in both circulating androgen and thymic CA levels are implicated in rat thymic involution. Its aims were to: i) explore putative effects of the late prepubertal orchidectomy on thymic CA:beta(2)-AR complex in young adult rats, and ii) delineate the direct effects of testicular hormone withdrawal on the CA:beta(2)-AR complex from those elicited secondarily through altered influence of this complex components on each other's availability. Upon showing that prepubertal orchidectomy augmented the efficacy of thymopoiesis through increasing the thymocyte surface density of Thy-1, whose expression is negatively regulated by beta(2)-AR-mediated signaling, we examined the effects of orchidectomy and 14-day-long propranolol (PROP) treatment in orchidectomized (ORX) and sham-ORX rats on thymic norepinephrine (NE) concentration and metabolism and beta(2)-AR expression. Orchidectomy, despite an increase in the average NE amount per thymocyte and total thymocyte NE content diminished thymic NE concentration. This decrease reflected the diminished density of CA-synthesizing nerve fibers, CD68 + macrophages, cortical (aminopeptidase A+), and medullary (UEA-1+) thymic epithelial cells (TECs) and their CA content (probably due to lessened TH expression accompanied by increased MAO-A expression). Moreover, orchidectomy decreased the surface beta(2)-AR expression on thymocytes, CD68+ macrophages and OX-62+ dendritic cells, but increased its expression on the TECs. In sham-ORX rats, PROP reduced thymic NE concentration by diminishing TH expression in the thymic cells. Additionally, PROP in thymocytes and thymic stromal cells diminished and enhanced the beta(2)-AR mRNA expression, respectively. However, in ORX rats PROP did not significantly affect CA(NE):beta(2)-AR complex components. This indicated that prepubertal orchidectomy affects ability of young adult rats to respond to beta-AR blockade by altering thymic NE and beta(2)-AR availability. Collectively, the results showed that testicular hormones contribute to alterations in thymus/thymopoiesis during the critical peripubertal period by shaping modulatory sympathetic influence and CA autocrine/paracrine action within the organ. (C) 2013 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis",
pages = "35-20",
number = "1-2",
volume = "265",
doi = "10.1016/j.jneuroim.2013.09.021"
}

Pilipović, I., Radojević, K., Kosec, D., Perišić-Nanut, M., Stojić-Vukanić, Z., Arsenović-Ranin, N.,& Leposavić, G.. (2013). Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis. in Journal of Neuroimmunology
Elsevier, Amsterdam., 265(1-2), 20-35.
https://doi.org/10.1016/j.jneuroim.2013.09.021

Pilipović I, Radojević K, Kosec D, Perišić-Nanut M, Stojić-Vukanić Z, Arsenović-Ranin N, Leposavić G. Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis. in Journal of Neuroimmunology. 2013;265(1-2):20-35.
doi:10.1016/j.jneuroim.2013.09.021 .

Pilipović, Ivan, Radojević, Katarina, Kosec, Duško, Perišić-Nanut, Milica, Stojić-Vukanić, Zorica, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Gonadal hormone dependent developmental plasticity of catecholamine:beta 2-adrenoceptor signaling complex in male rat thymus: Putative implications for thymopoiesis" in Journal of Neuroimmunology, 265, no. 1-2 (2013):20-35,
https://doi.org/10.1016/j.jneuroim.2013.09.021 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Stanojević, Stanislava
AU  - Kuštrimović, Nataša
AU  - Mitić, Katarina
AU  - Vujić, Vesna
AU  - Aleksić, Iva
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/383
AB  - The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-alpha and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17 beta-estradiol on LPS-induced macrophage TNF-alpha and NO production. Results showed that: ( a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-alpha, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-alpha production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-alpha and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. (C) 2013 Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production
EP  - 1254
IS  - 11
SP  - 1243
VL  - 48
DO  - 10.1016/j.exger.2013.07.001
ER  - 

@article{
author = "Dimitrijević, Mirjana and Stanojević, Stanislava and Kuštrimović, Nataša and Mitić, Katarina and Vujić, Vesna and Aleksić, Iva and Radojević, Katarina and Leposavić, Gordana",
year = "2013",
abstract = "The phenotype and function of tissue macrophages substantially depend on the cellular milieu and biological effector molecules, such as steroid hormones, to which they are exposed. Furthermore, in female rats, aging is associated with the altered macrophage functioning and the increased estrogen level is followed by a decrease in that of progesterone. Therefore, the present study aimed to investigate the influence of estradiol/progesterone balance on rat macrophage function and phenotype throughout whole adult lifespan. We ovariectomized rats at the late prepubertal age or at the very end of reproductive lifespan, and examined the expression of ED2 (CD163, a marker of mature resident macrophages related to secretion of inflammatory mediators) on peritoneal macrophages and their ability to produce TNF-alpha and NO upon LPS-stimulation at different age points. In addition, to delineate direct and indirect effects of estrogen, we assessed the in vitro influence of different concentrations of 17 beta-estradiol on LPS-induced macrophage TNF-alpha and NO production. Results showed that: ( a) the low frequency of ED2(high) cells amongst peritoneal macrophages of aged rats was accompanied with the reduced TNF-alpha, but not NO production; (b) estradiol level gradually increased following ovariectomy; (c) macrophage ED2 expression and TNF-alpha production were dependent on estradiol/progesterone balance and they changed in the same direction; (d) changes in estradiol/progesterone balance differentially affected macrophages TNF-alpha and NO production; and (e) estradiol exerted pro-inflammatory and anti-inflammatory effects on macrophages in vivo and in vitro, respectively. Overall, our study discloses that estradiol/progesterone balance contributes to the fine-tuning of rat macrophage secretory capacity, and adds to a better understanding of the ovarian steroid hormone role in the regulation of macrophage function, and its significance for the age-associated changes in innate immunity. (C) 2013 Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production",
pages = "1254-1243",
number = "11",
volume = "48",
doi = "10.1016/j.exger.2013.07.001"
}

Dimitrijević, M., Stanojević, S., Kuštrimović, N., Mitić, K., Vujić, V., Aleksić, I., Radojević, K.,& Leposavić, G.. (2013). The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 48(11), 1243-1254.
https://doi.org/10.1016/j.exger.2013.07.001

Dimitrijević M, Stanojević S, Kuštrimović N, Mitić K, Vujić V, Aleksić I, Radojević K, Leposavić G. The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production. in Experimental Gerontology. 2013;48(11):1243-1254.
doi:10.1016/j.exger.2013.07.001 .

Dimitrijević, Mirjana, Stanojević, Stanislava, Kuštrimović, Nataša, Mitić, Katarina, Vujić, Vesna, Aleksić, Iva, Radojević, Katarina, Leposavić, Gordana, "The influence of aging and estradiol to progesterone ratio on rat macrophage phenotypic profile and NO and TNF-alpha production" in Experimental Gerontology, 48, no. 11 (2013):1243-1254,
https://doi.org/10.1016/j.exger.2013.07.001 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Leposavić, Gordana
PY  - 2012
UR  - http://intor.torlakinstitut.com/handle/123456789/353
AB  - Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and beta(2)- and alpha(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of beta(2)- and alpha(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine beta-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of alpha(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation.
PB  - Wiley-Blackwell, Hoboken
T2  - Experimental Physiology
T1  - Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids
EP  - 1223
IS  - 11
SP  - 1211
VL  - 97
DO  - 10.1113/expphysiol.2012.064899
ER  - 

@article{
author = "Pilipović, Ivan and Radojević, Katarina and Perišić, Milica and Kosec, Duško and Nacka-Aleksić, Mirjana and Đikić, Jasmina and Leposavić, Gordana",
year = "2012",
abstract = "Glucocorticoids have been shown to modulate the expression of noradrenaline metabolizing enzymes and beta(2)- and alpha(1B)-adrenoceptors in a tissue- and cell- specific manner. In the thymus, apart from extensive sympathetic innervation, a regulatory network has been identified that encompasses catecholamine-containing non-lymphoid and lymphoid cells. We examined a putative role of adrenal- and thymus-derived glucocorticoids in modulation of rat thymic noradrenaline levels and adrenoceptor expression. Seven days postadrenalectomy, the thymic levels of mRNAs encoding tyrosine hydroxylase, dopamine beta-hydroxylase, monoamine oxidase-A and, consequently, noradrenaline were decreased. Catecholamine content was diminished in autofluorescent nerve fibres (judging by the intensity of fluorescence) and thymocytes (considering HPLC measurements of noradrenaline and the frequency of tyrosine hydroxylase-positive cells), while it remained unaltered in non-lymphoid autofluorescent cells. In addition, adrenalectomy diminished the thymocyte expression of beta(2)- and alpha(1B)-adrenoceptors at both mRNA and protein levels. Administration of ketoconazole (an inhibitor of glucocorticoid synthesis/action; 25 mg kg(-1) day(-1), s.c.) to glucocorticoid-deprived rats increased the thymic levels of tyrosine hydroxylase, dopamine beta-hydroxylase and, consequently, noradrenaline. The increased intensity of the autofluorescent cell fluorescence in ketoconazole-treated rats indicated an increase in their catecholamine content, and suggested differential glucocorticoid-mediated regulation of catecholamines in thymic lymphoid and non-lymphoid cells. In addition, ketoconazole increased the thymocyte expression of alpha(1B)-adrenoceptors. Thus, this study indicates that in the thymus, as in some other tissues, glucocorticoids not only act in concert with cateholamines, but they may modulate catecholamine action by tuning thymic catecholamine metabolism and adrenoceptor expression in a cell-specific manner. Additionally, the study indicates a role of thymus-derived glucocorticoids in this modulation.",
publisher = "Wiley-Blackwell, Hoboken",
journal = "Experimental Physiology",
title = "Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids",
pages = "1223-1211",
number = "11",
volume = "97",
doi = "10.1113/expphysiol.2012.064899"
}

Pilipović, I., Radojević, K., Perišić, M., Kosec, D., Nacka-Aleksić, M., Đikić, J.,& Leposavić, G.. (2012). Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids. in Experimental Physiology
Wiley-Blackwell, Hoboken., 97(11), 1211-1223.
https://doi.org/10.1113/expphysiol.2012.064899

Pilipović I, Radojević K, Perišić M, Kosec D, Nacka-Aleksić M, Đikić J, Leposavić G. Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids. in Experimental Physiology. 2012;97(11):1211-1223.
doi:10.1113/expphysiol.2012.064899 .

Pilipović, Ivan, Radojević, Katarina, Perišić, Milica, Kosec, Duško, Nacka-Aleksić, Mirjana, Đikić, Jasmina, Leposavić, Gordana, "Catecholaminergic signalling through thymic nerve fibres, thymocytes and stromal cells is dependent on both circulating and locally synthesized glucocorticoids" in Experimental Physiology, 97, no. 11 (2012):1211-1223,
https://doi.org/10.1113/expphysiol.2012.064899 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Perišić, Milica
AU  - Leposavić, Gordana
PY  - 2012
UR  - http://intor.torlakinstitut.com/handle/123456789/347
AB  - This paper highlights the multiple putative thymic and extrathymic points of intersection and interaction between glucocorticoids (GCs) and catecholamines (CAs)-the end-point mediators of the major routes of communication between the brain and the immune system-in the context of intricate thymic T cell-developmental tuning. More specifically, we discuss in detail findings indicating that adrenal GCs can influence thymopoiesis by adjusting directly and/or indirectly (through modulation of pituitary and local ACTH synthesis) not only thymic GC synthesis, in a cell type-specific manner, but also thymic CA bioavailability (via altering CA outflow from sympathetic nerve endings and local CA synthesis), beta and alpha(1)-adrenoceptor (AR) expression, and/or AR-mediated intracellular signal transduction in thymic cells. In addition, this short review points to GC-and CA-sensitive stages along the multistep T cell-developmental journey and the possible effects of altered GC, and consequently CA signaling, on thymopoietic efficiency.
PB  - Blackwell Science Publ, Oxford
T2  - Neuroimmunomodulation in Health and Disease I
T1  - Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network
EP  - 41
SP  - 34
VL  - 1261
DO  - 10.1111/j.1749-6632.2012.06623.x
ER  - 

@article{
author = "Pilipović, Ivan and Radojević, Katarina and Perišić, Milica and Leposavić, Gordana",
year = "2012",
abstract = "This paper highlights the multiple putative thymic and extrathymic points of intersection and interaction between glucocorticoids (GCs) and catecholamines (CAs)-the end-point mediators of the major routes of communication between the brain and the immune system-in the context of intricate thymic T cell-developmental tuning. More specifically, we discuss in detail findings indicating that adrenal GCs can influence thymopoiesis by adjusting directly and/or indirectly (through modulation of pituitary and local ACTH synthesis) not only thymic GC synthesis, in a cell type-specific manner, but also thymic CA bioavailability (via altering CA outflow from sympathetic nerve endings and local CA synthesis), beta and alpha(1)-adrenoceptor (AR) expression, and/or AR-mediated intracellular signal transduction in thymic cells. In addition, this short review points to GC-and CA-sensitive stages along the multistep T cell-developmental journey and the possible effects of altered GC, and consequently CA signaling, on thymopoietic efficiency.",
publisher = "Blackwell Science Publ, Oxford",
journal = "Neuroimmunomodulation in Health and Disease I",
title = "Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network",
pages = "41-34",
volume = "1261",
doi = "10.1111/j.1749-6632.2012.06623.x"
}

Pilipović, I., Radojević, K., Perišić, M.,& Leposavić, G.. (2012). Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network. in Neuroimmunomodulation in Health and Disease I
Blackwell Science Publ, Oxford., 1261, 34-41.
https://doi.org/10.1111/j.1749-6632.2012.06623.x

Pilipović I, Radojević K, Perišić M, Leposavić G. Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network. in Neuroimmunomodulation in Health and Disease I. 2012;1261:34-41.
doi:10.1111/j.1749-6632.2012.06623.x .

Pilipović, Ivan, Radojević, Katarina, Perišić, Milica, Leposavić, Gordana, "Glucocorticoid-catecholamine interplay within the composite thymopoietic regulatory network" in Neuroimmunomodulation in Health and Disease I, 1261 (2012):34-41,
https://doi.org/10.1111/j.1749-6632.2012.06623.x . .

TY  - JOUR
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Perišić, Milica
AU  - Pilipović, Ivan
AU  - Vidić-Danković, Biljana
AU  - Leposavić, Gordana
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/333
AB  - We tested the hypothesis that neonatal androgenization affects the efficacy of beta-adrenoceptor (beta-AR)-mediated fine tuning of thymopoiesis in adult female rats by modulating the thymic noradrenaline (NA) level and/or beta-AR expression. In adult rats administered with 1000 mu g testosterone enanthate at postnatal day 2 a higher density of catecholamine (CA)-synthesizing thymic cells, including thymocytes, and a rise in their CA content was found. In addition, in these animals increased thymic noradrenergic nerve fiber fluorescence intensity, reflecting their increased CA content, was detected. These changes were followed by an increase in thymic NA concentration. The rise in thymic NA content in thymic nerve fibers and cells was associated with changes in the expression of mRNA for enzymes controling pivotal steps in NA biosynthesis (tyrosine hydroxylase, dopamine-beta-hydroxylase) and inactivation (monoamine oxidase). In contrast, the thymic level of beta(2)-AR mRNA on a per cell basis and the receptor surface density on thymocytes was reduced in testosterone-treated (TT) rats. As a consequence, 14-day-long treatment with propranolol, a beta-AR blocker, was ineffective in modulating T-cell differentiation/maturation in TT rats. In conclusion, the study indicates the importance of the neonatal sex steroid milieu for shaping the immunomodulatory capacity of the thymic NA/beta-AR signaling system in adult rats. (C) 2011 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis
EP  - 79
IS  - 1-2
SP  - 68
VL  - 239
DO  - 10.1016/j.jneuroim.2011.08.020
ER  - 

@article{
author = "Radojević, Katarina and Kosec, Duško and Perišić, Milica and Pilipović, Ivan and Vidić-Danković, Biljana and Leposavić, Gordana",
year = "2011",
abstract = "We tested the hypothesis that neonatal androgenization affects the efficacy of beta-adrenoceptor (beta-AR)-mediated fine tuning of thymopoiesis in adult female rats by modulating the thymic noradrenaline (NA) level and/or beta-AR expression. In adult rats administered with 1000 mu g testosterone enanthate at postnatal day 2 a higher density of catecholamine (CA)-synthesizing thymic cells, including thymocytes, and a rise in their CA content was found. In addition, in these animals increased thymic noradrenergic nerve fiber fluorescence intensity, reflecting their increased CA content, was detected. These changes were followed by an increase in thymic NA concentration. The rise in thymic NA content in thymic nerve fibers and cells was associated with changes in the expression of mRNA for enzymes controling pivotal steps in NA biosynthesis (tyrosine hydroxylase, dopamine-beta-hydroxylase) and inactivation (monoamine oxidase). In contrast, the thymic level of beta(2)-AR mRNA on a per cell basis and the receptor surface density on thymocytes was reduced in testosterone-treated (TT) rats. As a consequence, 14-day-long treatment with propranolol, a beta-AR blocker, was ineffective in modulating T-cell differentiation/maturation in TT rats. In conclusion, the study indicates the importance of the neonatal sex steroid milieu for shaping the immunomodulatory capacity of the thymic NA/beta-AR signaling system in adult rats. (C) 2011 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis",
pages = "79-68",
number = "1-2",
volume = "239",
doi = "10.1016/j.jneuroim.2011.08.020"
}

Radojević, K., Kosec, D., Perišić, M., Pilipović, I., Vidić-Danković, B.,& Leposavić, G.. (2011). Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis. in Journal of Neuroimmunology
Elsevier Science Bv, Amsterdam., 239(1-2), 68-79.
https://doi.org/10.1016/j.jneuroim.2011.08.020

Radojević K, Kosec D, Perišić M, Pilipović I, Vidić-Danković B, Leposavić G. Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis. in Journal of Neuroimmunology. 2011;239(1-2):68-79.
doi:10.1016/j.jneuroim.2011.08.020 .

Radojević, Katarina, Kosec, Duško, Perišić, Milica, Pilipović, Ivan, Vidić-Danković, Biljana, Leposavić, Gordana, "Neonatal androgenization affects the efficiency of beta-adrenoceptor-mediated modulation of thymopoiesis" in Journal of Neuroimmunology, 239, no. 1-2 (2011):68-79,
https://doi.org/10.1016/j.jneuroim.2011.08.020 . .

TY  - CONF
AU  - Perišić, Milica
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/330
PB  - Karger, Basel
C3  - Neuroimmunomodulation
T1  - Ovarian Hormones Control Pace of Age-Related Remodelling of T-cell Population from Puberty to Middle-Age
EP  - 397
IS  - 6
SP  - 397
VL  - 18
UR  - https://hdl.handle.net/21.15107/rcub_intor_330
ER  - 

@conference{
author = "Perišić, Milica and Stojić-Vukanić, Zorica and Pilipović, Ivan and Radojević, Katarina and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2011",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Ovarian Hormones Control Pace of Age-Related Remodelling of T-cell Population from Puberty to Middle-Age",
pages = "397-397",
number = "6",
volume = "18",
url = "https://hdl.handle.net/21.15107/rcub_intor_330"
}

Perišić, M., Stojić-Vukanić, Z., Pilipović, I., Radojević, K., Arsenović-Ranin, N.,& Leposavić, G.. (2011). Ovarian Hormones Control Pace of Age-Related Remodelling of T-cell Population from Puberty to Middle-Age. in Neuroimmunomodulation
Karger, Basel., 18(6), 397-397.
https://hdl.handle.net/21.15107/rcub_intor_330

Perišić M, Stojić-Vukanić Z, Pilipović I, Radojević K, Arsenović-Ranin N, Leposavić G. Ovarian Hormones Control Pace of Age-Related Remodelling of T-cell Population from Puberty to Middle-Age. in Neuroimmunomodulation. 2011;18(6):397-397.
https://hdl.handle.net/21.15107/rcub_intor_330 .

Perišić, Milica, Stojić-Vukanić, Zorica, Pilipović, Ivan, Radojević, Katarina, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Ovarian Hormones Control Pace of Age-Related Remodelling of T-cell Population from Puberty to Middle-Age" in Neuroimmunomodulation, 18, no. 6 (2011):397-397,
https://hdl.handle.net/21.15107/rcub_intor_330 .

TY  - CONF
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Perišić, Milica
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Leposavić, Gordana
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/318
PB  - Karger, Basel
C3  - Neuroimmunomodulation
T1  - Circulating and Thymic-Derived Glucocorticoids Influence Expression of Key Enzymes Controlling the Metabolism of Catecholamines and Adrenoceptors in Thymocytes
EP  - 398
IS  - 6
SP  - 398
VL  - 18
UR  - https://hdl.handle.net/21.15107/rcub_intor_318
ER  - 

@conference{
author = "Pilipović, Ivan and Radojević, Katarina and Perišić, Milica and Nacka-Aleksić, Mirjana and Đikić, Jasmina and Leposavić, Gordana",
year = "2011",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Circulating and Thymic-Derived Glucocorticoids Influence Expression of Key Enzymes Controlling the Metabolism of Catecholamines and Adrenoceptors in Thymocytes",
pages = "398-398",
number = "6",
volume = "18",
url = "https://hdl.handle.net/21.15107/rcub_intor_318"
}

Pilipović, I., Radojević, K., Perišić, M., Nacka-Aleksić, M., Đikić, J.,& Leposavić, G.. (2011). Circulating and Thymic-Derived Glucocorticoids Influence Expression of Key Enzymes Controlling the Metabolism of Catecholamines and Adrenoceptors in Thymocytes. in Neuroimmunomodulation
Karger, Basel., 18(6), 398-398.
https://hdl.handle.net/21.15107/rcub_intor_318

Pilipović I, Radojević K, Perišić M, Nacka-Aleksić M, Đikić J, Leposavić G. Circulating and Thymic-Derived Glucocorticoids Influence Expression of Key Enzymes Controlling the Metabolism of Catecholamines and Adrenoceptors in Thymocytes. in Neuroimmunomodulation. 2011;18(6):398-398.
https://hdl.handle.net/21.15107/rcub_intor_318 .

Pilipović, Ivan, Radojević, Katarina, Perišić, Milica, Nacka-Aleksić, Mirjana, Đikić, Jasmina, Leposavić, Gordana, "Circulating and Thymic-Derived Glucocorticoids Influence Expression of Key Enzymes Controlling the Metabolism of Catecholamines and Adrenoceptors in Thymocytes" in Neuroimmunomodulation, 18, no. 6 (2011):398-398,
https://hdl.handle.net/21.15107/rcub_intor_318 .

TY  - JOUR
AU  - Perišić, Milica
AU  - Arsenović-Ranin, Nevena
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Pešić, Vesna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2010
UR  - http://intor.torlakinstitut.com/handle/123456789/304
AB  - A commonly held view that ovarian hormones are causally involved in age-associated thymic involution has been recently challenged. In particular, their relevance in the progression of thymic involution has been disputed. To reassess this issue 10-month-old rats with well advanced thymic involutive changes were ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development and levels of recent thymic emigrants (RTEs) were examined in peripheral blood and spleen. In addition, the distribution of major conventional and regulatory T-cell subsets was analyzed in the same peripheral lymphocyte compartments. Ovariectomy increased thymic weight and cellularity above the levels in both 10-month-old and age-matched controls indicating that ovarian hormone ablation not only prevented further progression of thymic involution, hut also reversed it. The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of nave T cells as indicated by elevated levels of both CD4 + and CD8 + RTEs in peripheral blood and spleen. The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4 + CD8 + T cell receptor (TCR)alpha beta(low) stage were reduced; the relative numbers of CD4 + CD8 + TCR alpha beta(low) cells entering positive selection and their immediate CD4 + CD8 + TCR alpha beta(high) descendents were increased, while those of the most mature CD4 + CD8 and CD4 CD8 + TCR alpha beta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4 + CD8 + thymocyte subset. The augmented thymic output of naive T cells in Ovx rats most likely reflected an early disinhibition of thymocyte development followed by increased positive/reduced negative selection, at least partly, due to raised thymocyte surface Thy-1 expression. The greater number of CD4 + CD25 + Foxp3 + cells in both thymus and peripheral blood suggested augmented thymic production of these cells. In addition, an increased CD4 + /CD8 + cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone ablation led not only to increased diversity of the T-cell repertoire, but also to a new balance among distinct T-cell subsets in the periphery. (C) 2009 Elsevier GmbH. All rights reserved.
PB  - Elsevier Gmbh, Munich
T2  - Immunobiology
T1  - Role of ovarian hormones in age-associated thymic involution revisited
EP  - 293
IS  - 4
SP  - 275
VL  - 215
DO  - 10.1016/j.imbio.2009.06.012
ER  - 

@article{
author = "Perišić, Milica and Arsenović-Ranin, Nevena and Pilipović, Ivan and Kosec, Duško and Pešić, Vesna and Radojević, Katarina and Leposavić, Gordana",
year = "2010",
abstract = "A commonly held view that ovarian hormones are causally involved in age-associated thymic involution has been recently challenged. In particular, their relevance in the progression of thymic involution has been disputed. To reassess this issue 10-month-old rats with well advanced thymic involutive changes were ovariectomized (Ovx), and after 1 month thymic cellularity, thymocyte development and levels of recent thymic emigrants (RTEs) were examined in peripheral blood and spleen. In addition, the distribution of major conventional and regulatory T-cell subsets was analyzed in the same peripheral lymphocyte compartments. Ovariectomy increased thymic weight and cellularity above the levels in both 10-month-old and age-matched controls indicating that ovarian hormone ablation not only prevented further progression of thymic involution, hut also reversed it. The increased thymic cellularity was accompanied by altered thymocyte differentiation/maturation culminating in increased thymic output of nave T cells as indicated by elevated levels of both CD4 + and CD8 + RTEs in peripheral blood and spleen. The changes in T-cell development produced: (i) a disproportional increase in cellularity across thymocyte subsets, so that relative proportions of cells at all maturational stages preceding the CD4 + CD8 + T cell receptor (TCR)alpha beta(low) stage were reduced; the relative numbers of CD4 + CD8 + TCR alpha beta(low) cells entering positive selection and their immediate CD4 + CD8 + TCR alpha beta(high) descendents were increased, while those of the most mature CD4 + CD8 and CD4 CD8 + TCR alpha beta(high) cells remained unaltered; (ii) enhanced cell proliferation across all thymocyte subsets and (iii) reduced apoptosis of cells within the CD4 + CD8 + thymocyte subset. The augmented thymic output of naive T cells in Ovx rats most likely reflected an early disinhibition of thymocyte development followed by increased positive/reduced negative selection, at least partly, due to raised thymocyte surface Thy-1 expression. The greater number of CD4 + CD25 + Foxp3 + cells in both thymus and peripheral blood suggested augmented thymic production of these cells. In addition, an increased CD4 + /CD8 + cell ratio was found in the spleen of Ovx rats. Thus, ovarian hormone ablation led not only to increased diversity of the T-cell repertoire, but also to a new balance among distinct T-cell subsets in the periphery. (C) 2009 Elsevier GmbH. All rights reserved.",
publisher = "Elsevier Gmbh, Munich",
journal = "Immunobiology",
title = "Role of ovarian hormones in age-associated thymic involution revisited",
pages = "293-275",
number = "4",
volume = "215",
doi = "10.1016/j.imbio.2009.06.012"
}

Perišić, M., Arsenović-Ranin, N., Pilipović, I., Kosec, D., Pešić, V., Radojević, K.,& Leposavić, G.. (2010). Role of ovarian hormones in age-associated thymic involution revisited. in Immunobiology
Elsevier Gmbh, Munich., 215(4), 275-293.
https://doi.org/10.1016/j.imbio.2009.06.012

Perišić M, Arsenović-Ranin N, Pilipović I, Kosec D, Pešić V, Radojević K, Leposavić G. Role of ovarian hormones in age-associated thymic involution revisited. in Immunobiology. 2010;215(4):275-293.
doi:10.1016/j.imbio.2009.06.012 .

Perišić, Milica, Arsenović-Ranin, Nevena, Pilipović, Ivan, Kosec, Duško, Pešić, Vesna, Radojević, Katarina, Leposavić, Gordana, "Role of ovarian hormones in age-associated thymic involution revisited" in Immunobiology, 215, no. 4 (2010):275-293,
https://doi.org/10.1016/j.imbio.2009.06.012 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Perišić, Milica
AU  - Pešić, Vesna
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2010
UR  - http://intor.torlakinstitut.com/handle/123456789/303
AB  - There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P  lt  0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P  lt  0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P  lt  0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.
PB  - Assoc Bras Divulg Cientifica, Ribeirao Preto
T2  - Brazilian Journal of Medical and Biological Research
T1  - Glucocorticoids, master modulators of the thymic catecholaminergic system?
EP  - 284
IS  - 3
SP  - 279
VL  - 43
DO  - 10.1590/S0100-879X2010007500005
ER  - 

@article{
author = "Pilipović, Ivan and Kosec, Duško and Radojević, Katarina and Perišić, Milica and Pešić, Vesna and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2010",
abstract = "There is evidence that the major mediators of stress, i.e., catecholamines and glucocorticoids, play an important role in modulating thymopoiesis and consequently immune responses. Furthermore, there are data suggesting that glucocorticoids influence catecholamine action. Therefore, to assess the putative relevance of glucocorticoid-catecholamine interplay in the modulation of thymopoiesis we analyzed thymocyte differentiation/maturation in non-adrenalectomized and andrenalectomized rats subjected to treatment with propranolol (0.4 mg.100 g body weight(-1).day(-1)) for 4 days. The effects of beta-adrenoceptor blockade on thymopoiesis in non-adrenalectomized rats differed not only quantitatively but also qualitatively from those in adrenalectomized rats. In adrenalectomized rats, besides a more efficient thymopoiesis [judged by a more pronounced increase in the relative proportion of the most mature single-positive TCR alpha beta(high) thymocytes as revealed by two-way ANOVA; for CD4(+)CD8(-)F (1,20) = 10.92, P  lt  0.01; for CD4(-)CD8(+)F (1,20) = 7.47, P  lt  0.05], a skewed thymocyte maturation towards the CD4(-)CD8(+) phenotype, and consequently a diminished CD4(+)CD8(-)/CD4(-)CD8(+) mature TCR alpha beta(high) thymocyte ratio (3.41 +/- 0.21 in non-adrenalectomized rats vs 2.90 +/- 0.31 in adrenalectomized rats, P  lt  0.05) were found. Therefore, we assumed that catecholaminergic modulation of thymopoiesis exhibits a substantial degree of glucocorticoid-dependent plasticity. Given that glucocorticoids, apart from catecholamine synthesis, influence adrenoceptor expression, we also hypothesized that the lack of adrenal glucocorticoids affected not only beta-adrenoceptor- but also alpha-adrenoceptor-mediated modulation of thymopoiesis.",
publisher = "Assoc Bras Divulg Cientifica, Ribeirao Preto",
journal = "Brazilian Journal of Medical and Biological Research",
title = "Glucocorticoids, master modulators of the thymic catecholaminergic system?",
pages = "284-279",
number = "3",
volume = "43",
doi = "10.1590/S0100-879X2010007500005"
}

Pilipović, I., Kosec, D., Radojević, K., Perišić, M., Pešić, V., Stojić-Vukanić, Z.,& Leposavić, G.. (2010). Glucocorticoids, master modulators of the thymic catecholaminergic system?. in Brazilian Journal of Medical and Biological Research
Assoc Bras Divulg Cientifica, Ribeirao Preto., 43(3), 279-284.
https://doi.org/10.1590/S0100-879X2010007500005

Pilipović I, Kosec D, Radojević K, Perišić M, Pešić V, Stojić-Vukanić Z, Leposavić G. Glucocorticoids, master modulators of the thymic catecholaminergic system?. in Brazilian Journal of Medical and Biological Research. 2010;43(3):279-284.
doi:10.1590/S0100-879X2010007500005 .

Pilipović, Ivan, Kosec, Duško, Radojević, Katarina, Perišić, Milica, Pešić, Vesna, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Glucocorticoids, master modulators of the thymic catecholaminergic system?" in Brazilian Journal of Medical and Biological Research, 43, no. 3 (2010):279-284,
https://doi.org/10.1590/S0100-879X2010007500005 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pešić, Vesna
AU  - Stojić-Vukanić, Zorica
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Perišić, Milica
AU  - Pilipović, Ivan
PY  - 2010
UR  - http://intor.torlakinstitut.com/handle/123456789/296
AB  - Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis. (C) 2010 Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development
EP  - 935
IS  - 12
SP  - 918
VL  - 45
DO  - 10.1016/j.exger.2010.08.011
ER  - 

@article{
author = "Leposavić, Gordana and Pešić, Vesna and Stojić-Vukanić, Zorica and Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Perišić, Milica and Pilipović, Ivan",
year = "2010",
abstract = "Alpha(1)-adrenoceptors (alpha(1)-ARs) are involved in neuro-thymic and thymic intercellular communications, and consequently modulation of T-cell development. Ageing is associated with a number of changes in noradrenergic neuro-effector transmission, and possibly intercellular noradrenaline (NA)-mediated communication resulting in altered responses of target cells to NA. Thus, in old animals an altered NA modulation of thymopoiesis via alpha(1)-ARs may be expected. To test this hypothesis, in old and young adult Wistar rats we examined: 1) thymic NA levels, density of noradrenergic innervation and NA synthesizing cells, as well as alpha(1)-AR expression, and 2) then the effects of 14-day-long treatment with the alpha(1)-AR blocker, urapidil, on thymocyte development. Overall, the first part of study suggested augmented NA signalling to thymic cells via alpha(1)-ARs due to increased NA availability and alpha(1)-AR thymocyte surface density in old rats. The second part of study supported this assumption. Namely, although in rats of both ages urapidil affected the same thymocyte developmental steps ultimately leading to changes in the relative number of the most mature single positive TCR alpha beta(high) thymocytes, its effects were generally more prominent in old animals. Following urapidil treatment, the percentages of CD4+CD8- cells, including those showing a regulatory CD4+CD25+RT6.1- phenotype, were increased, while CD4-CD8+ cells decreased. In old rats, an augmented thymic escape of immature CD4+CD8+ cells was also registered. In rats of both ages the thymic changes were accompanied by alterations in the proportions of major cell populations in the T-lymphocyte compartment of both peripheral blood and spleen, leading to an increase in the CD4+/CD8+ T-cell ratio. These alterations were also more pronounced in old rats. Moreover, in old rats following urapidil treatment the proportion of TCR alpha beta + cells in the periphery was slightly greater reflecting, most likely, partly enhanced thymic production of regulatory CD161 +TCR alpha beta + cells. Thus, the study indirectly suggests an age-associated increase in the basal alpha(1)-AR-mediated inhibitory influence of NA on thymopoiesis. (C) 2010 Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development",
pages = "935-918",
number = "12",
volume = "45",
doi = "10.1016/j.exger.2010.08.011"
}

Leposavić, G., Pešić, V., Stojić-Vukanić, Z., Radojević, K., Arsenović-Ranin, N., Kosec, D., Perišić, M.,& Pilipović, I.. (2010). Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 45(12), 918-935.
https://doi.org/10.1016/j.exger.2010.08.011

Leposavić G, Pešić V, Stojić-Vukanić Z, Radojević K, Arsenović-Ranin N, Kosec D, Perišić M, Pilipović I. Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development. in Experimental Gerontology. 2010;45(12):918-935.
doi:10.1016/j.exger.2010.08.011 .

Leposavić, Gordana, Pešić, Vesna, Stojić-Vukanić, Zorica, Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Perišić, Milica, Pilipović, Ivan, "Age-associated plasticity of alpha 1-adrenoceptor-mediated tuning of T-cell development" in Experimental Gerontology, 45, no. 12 (2010):918-935,
https://doi.org/10.1016/j.exger.2010.08.011 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Arsenović-Ranin, Nevena
AU  - Radojević, Katarina
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
PY  - 2009
UR  - http://intor.torlakinstitut.com/handle/123456789/289
AB  - Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. (C) 2008 Elsevier Inc. All rights reserved.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats
EP  - 304
IS  - 2
SP  - 294
VL  - 23
DO  - 10.1016/j.bbi.2008.11.002
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica and Kosec, Duško and Arsenović-Ranin, Nevena and Radojević, Katarina and Stojić-Vukanić, Zorica and Pilipović, Ivan",
year = "2009",
abstract = "Exposure of female rodents to testosterone in the critical neonatal period produces defeminization/masculinization of the hypothalamo-pituitary-gonadal (HPG) axis, i.e. neonatal androgenization and postpones axis maturation. To address the hypothesis that HPG axis signaling is involved in the programming of thymic maturation/involution and sexual differentiation we studied the impact of neonatal androgenization on thymic cellularity, development of effector and regulatory T cells, and phenotypic characteristics of peripheral blood T lymphocytes in adult rats. A single injection of testosterome on postnatal day 2 postponed thymic maturation/involution as revealed by organ hypercellularity, increased cellularity of the most mature (CD4+CD8- and CD4-CD8+) TCR alpha beta(high) thymocyte and both recent thymic emigrant (RTE) subsets and caused phenotypic efeminization/masculinization of thymic (decreased CD4+CD8-TCR alpha beta(high)/CD4-CD8+TCR alpha beta(high) cell ratio) and peripheral blood T-cell compartments (decreased CD4+RTE/CD8+RTE and CD4+/CD8+ cell ratio). In addition, neonatal androgenization increased the relative and absolute numbers of both CD4+CD25+Foxp3+ and natural killer (NK) regulatory T cells in peripheral blood. These findings, in conjunction with thymocyte overexpression of Thy-1 that is assumed to reduce negative selection affecting self-reactive cell generation, suggest a new relationship between self-reactive and regulatory T cells. In conclusion, our study provides additional evidence for a role of HPG signals (i.e. sex steroids and gonadotropins) in programming the kinetics of thymic maturation/involution and in establishing immunological sexual dimorphism. (C) 2008 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats",
pages = "304-294",
number = "2",
volume = "23",
doi = "10.1016/j.bbi.2008.11.002"
}

Leposavić, G., Perišić, M., Kosec, D., Arsenović-Ranin, N., Radojević, K., Stojić-Vukanić, Z.,& Pilipović, I.. (2009). Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 23(2), 294-304.
https://doi.org/10.1016/j.bbi.2008.11.002

Leposavić G, Perišić M, Kosec D, Arsenović-Ranin N, Radojević K, Stojić-Vukanić Z, Pilipović I. Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats. in Brain Behavior and Immunity. 2009;23(2):294-304.
doi:10.1016/j.bbi.2008.11.002 .

Leposavić, Gordana, Perišić, Milica, Kosec, Duško, Arsenović-Ranin, Nevena, Radojević, Katarina, Stojić-Vukanić, Zorica, Pilipović, Ivan, "Neonatal testosterone imprinting affects thymus development and leads to phenotypic rejuvenation and masculinization of the peripheral blood T-cell compartment in adult female rats" in Brain Behavior and Immunity, 23, no. 2 (2009):294-304,
https://doi.org/10.1016/j.bbi.2008.11.002 . .

TY  - JOUR
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Rakin, Ana
AU  - Leposavić, Gordana
PY  - 2009
UR  - http://intor.torlakinstitut.com/handle/123456789/288
AB  - The present study was undertaken to reassess the recently challenged role of ovarian hormones in age-associated thymic involution. For this purpose, in eleven-month-old peripubertally ovariectomized (Ox) rats we analyzed: i) thymic weight and cellularity, ii) size of CD4+CD8+ double-positive (DP) thymocyte population, which is believed to correlate to the thymic capacity to export mature T cells, iii) number of recent thymic emigrants (RTEs), and iv) number of peripheral blood CD4+ and CD8+ lymphocytes. It was found that both thymic weight and cellularity were greater in Ox than in control rats. In addition, in Ox rats the numbers of DP thymocytes and both CD4+ and CD8+ RTEs, were significantly greater than in controls, indicating a more efficient generation of T cells in these rats. Furthermore, these findings, coupled with data indicating that the number of neither CD4+ nor CD8+ peripheral blood lymphocytes was affected by ovariectomy, most likely, suggest a reduced homeostatic proliferation of memory cells in Ox rats, i.e. broadening of TCR peripheral repertoire without changes in the overall number of T cells leading to a more efficient response to newly encountered antigens. The results indicate that the ovarian steroid deprivation from early peripubertal period leads to a long lasting postponement/alleviation of age-associated decline in T-cell mediated immune response.
AB  - Ova istraživanja su preduzeta sa ciljem da se preispita uloga gonadnih hormona u involuciji timusa, koja je nedavno dovedena u pitanje. U tom cilju je kod 11 meseci starih ženki pacova, koje su ovarijektomisane (Ox) u peripubertetnom uzrastu, analizirana: i) težina i celularnost timusa, ii) broj CD4+CD8+ dvostruko pozitivnih (DP) timocita, za koji se smatra da odražavaju sposobnost organa da generiše zrele T limfocite, iii) broj neposrednih emigranata iz timusa (RTE) i iv) ukupan broj CD4+ i CD8+ limfocita u perifernoj krvi. Dokazano je da su težina i celularnost timusa bile značajno veće u Ox životinja. Kod ovih životinja je nađen i povećan broj DP timocita, kao i CD4+ i CD8+ RTE, što ukazuje na efikasniju produkciju T ćelija u njihovom timusu. Ovaj nalaz, u kontekstu nepromenjenog broja CD4+ i CD8+ ćelija u perifernoj krvi, takođe sugeriše smanjenu homeostatsku proliferaciju memorijskih ćelija, odnosno ukazuje na kvalitativne promene u perifernom T ćelijskom repertoaru (koje obezbeđuju efikasniji odgovor na nove antigene) bez kvantitativnih promena. U celini, rezultati ukazuju da u odsustvu hormona ovarijuma počevši od ranog peripubertetnog uzrasta dolazi do značajnog odlaganja/ublažavanja involucije timusa i posledičnih promena na periferiji.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria - Beograd
T1  - Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output
T1  - Peripubertetna ovarijektomija obezbeđuje dugotrajno odlaganje starenjem uslovljenog smanjenja celularnosti timusa i produkcije T limfocita
EP  - 15
IS  - 1
SP  - 3
VL  - 59
DO  - 10.2298/AVB0901003P
ER  - 

@article{
author = "Perišić, Milica and Kosec, Duško and Pilipović, Ivan and Radojević, Katarina and Pešić, Vesna and Rakin, Ana and Leposavić, Gordana",
year = "2009",
abstract = "The present study was undertaken to reassess the recently challenged role of ovarian hormones in age-associated thymic involution. For this purpose, in eleven-month-old peripubertally ovariectomized (Ox) rats we analyzed: i) thymic weight and cellularity, ii) size of CD4+CD8+ double-positive (DP) thymocyte population, which is believed to correlate to the thymic capacity to export mature T cells, iii) number of recent thymic emigrants (RTEs), and iv) number of peripheral blood CD4+ and CD8+ lymphocytes. It was found that both thymic weight and cellularity were greater in Ox than in control rats. In addition, in Ox rats the numbers of DP thymocytes and both CD4+ and CD8+ RTEs, were significantly greater than in controls, indicating a more efficient generation of T cells in these rats. Furthermore, these findings, coupled with data indicating that the number of neither CD4+ nor CD8+ peripheral blood lymphocytes was affected by ovariectomy, most likely, suggest a reduced homeostatic proliferation of memory cells in Ox rats, i.e. broadening of TCR peripheral repertoire without changes in the overall number of T cells leading to a more efficient response to newly encountered antigens. The results indicate that the ovarian steroid deprivation from early peripubertal period leads to a long lasting postponement/alleviation of age-associated decline in T-cell mediated immune response., Ova istraživanja su preduzeta sa ciljem da se preispita uloga gonadnih hormona u involuciji timusa, koja je nedavno dovedena u pitanje. U tom cilju je kod 11 meseci starih ženki pacova, koje su ovarijektomisane (Ox) u peripubertetnom uzrastu, analizirana: i) težina i celularnost timusa, ii) broj CD4+CD8+ dvostruko pozitivnih (DP) timocita, za koji se smatra da odražavaju sposobnost organa da generiše zrele T limfocite, iii) broj neposrednih emigranata iz timusa (RTE) i iv) ukupan broj CD4+ i CD8+ limfocita u perifernoj krvi. Dokazano je da su težina i celularnost timusa bile značajno veće u Ox životinja. Kod ovih životinja je nađen i povećan broj DP timocita, kao i CD4+ i CD8+ RTE, što ukazuje na efikasniju produkciju T ćelija u njihovom timusu. Ovaj nalaz, u kontekstu nepromenjenog broja CD4+ i CD8+ ćelija u perifernoj krvi, takođe sugeriše smanjenu homeostatsku proliferaciju memorijskih ćelija, odnosno ukazuje na kvalitativne promene u perifernom T ćelijskom repertoaru (koje obezbeđuju efikasniji odgovor na nove antigene) bez kvantitativnih promena. U celini, rezultati ukazuju da u odsustvu hormona ovarijuma počevši od ranog peripubertetnog uzrasta dolazi do značajnog odlaganja/ublažavanja involucije timusa i posledičnih promena na periferiji.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria - Beograd",
title = "Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output, Peripubertetna ovarijektomija obezbeđuje dugotrajno odlaganje starenjem uslovljenog smanjenja celularnosti timusa i produkcije T limfocita",
pages = "15-3",
number = "1",
volume = "59",
doi = "10.2298/AVB0901003P"
}

Perišić, M., Kosec, D., Pilipović, I., Radojević, K., Pešić, V., Rakin, A.,& Leposavić, G.. (2009). Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output. in Acta veterinaria - Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 59(1), 3-15.
https://doi.org/10.2298/AVB0901003P

Perišić M, Kosec D, Pilipović I, Radojević K, Pešić V, Rakin A, Leposavić G. Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output. in Acta veterinaria - Beograd. 2009;59(1):3-15.
doi:10.2298/AVB0901003P .

Perišić, Milica, Kosec, Duško, Pilipović, Ivan, Radojević, Katarina, Pešić, Vesna, Rakin, Ana, Leposavić, Gordana, "Peripubertal ovariectomy provides long-term postponement of age-associated decline in thymic cellularity and T-cell output" in Acta veterinaria - Beograd, 59, no. 1 (2009):3-15,
https://doi.org/10.2298/AVB0901003P . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Rauški, Aleksandra
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2009
UR  - http://intor.torlakinstitut.com/handle/123456789/282
AB  - A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009
PB  - Sage Publications Ltd, London
T2  - Experimental Biology and Medicine
T1  - Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats
EP  - 1074
IS  - 9
SP  - 1067
VL  - 234
DO  - 10.3181/0902-RM-63
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Rauški, Aleksandra and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Leposavić, Gordana",
year = "2009",
abstract = "A number of different experimental approaches have been used to elucidate the impact: of basal levels of adrenal gland-derived glucocorticoids (GCs) on T cell development, and thereby T cell-mediated immune responses. However, the relevance of the adrenal GCs to T cell development is still far from clear. This study was undertaken to explore the relevance of basal levels of GCs to T cell differentiation/maturation. Eight days post-adrenalectomy in adult male rats the thymocyte yield, apoptotic and proliferative rate and the relationship amongst major thymocyte subsets, as defined by TCR alpha beta/CD4/CD8 expression, were examined using flow cytometry. Adrenal GC deprivation decreased thymocyte apoptosis and altered the kinetics of T cell differentiation/maturation. In the adrenalectomized rats there was increased thymic hypercellularity and an over-representation of the CD4+CD8+ double positive (DP) TCR alpha beta(low) cells entering selection, as well as increased numbers of their DP TCR alpha beta(-) immediate precursors. These changes were accompanied with under-representation of the postselected DP TCR alpha beta(high) and the most mature CD4-CD8+ and, particularly, CD4+CD8-single positive (SP) TCR alpha beta(high) cells. This data suggests that withdrawal of adrenal GCs produces alterations in the thymocyte selection processes, possibly affecting the diversity of functional T cell repertoire and generation of potentially self-reactive cells as indicated by the reduced proportion and number of CD4-CD8- double negative TCR alpha beta(high) cells. In addition, it indicates that GCs influence the post-selection maturation of thymocytes and plays a regulatory role in controlling the ratio of mature CD4+CD8-/CD4-CD8+ SP TCR alpha beta(high) cells. Exp Biol Med 234:1067-1074, 2009",
publisher = "Sage Publications Ltd, London",
journal = "Experimental Biology and Medicine",
title = "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats",
pages = "1074-1067",
number = "9",
volume = "234",
doi = "10.3181/0902-RM-63"
}

Stojić-Vukanić, Z., Rauški, A., Kosec, D., Radojević, K., Pilipović, I.,& Leposavić, G.. (2009). Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine
Sage Publications Ltd, London., 234(9), 1067-1074.
https://doi.org/10.3181/0902-RM-63

Stojić-Vukanić Z, Rauški A, Kosec D, Radojević K, Pilipović I, Leposavić G. Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats. in Experimental Biology and Medicine. 2009;234(9):1067-1074.
doi:10.3181/0902-RM-63 .

Stojić-Vukanić, Zorica, Rauški, Aleksandra, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Leposavić, Gordana, "Dysregulation of T-Cell Development in Adrenal Glucocorticoid-Deprived Rats" in Experimental Biology and Medicine, 234, no. 9 (2009):1067-1074,
https://doi.org/10.3181/0902-RM-63 . .

TY  - JOUR
AU  - Pešić, Vesna
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Vidić-Danković, Biljana
AU  - Leposavić, Gordana
PY  - 2009
UR  - http://intor.torlakinstitut.com/handle/123456789/272
AB  - The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCR alpha beta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCR alpha beta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCR alpha beta(high) high thymocytes. In urapidil-administered rats the percentage of CD4+CD8-SP TCR alpha beta(high) thymocytes was increased, while that of the CD4-CD8+ TCR alpha beta(high) was reduced. compared with controls. In addition, proportions of CD4+CD25+ RT6.1- and CD161+TCR alpha beta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development. (c) 2009 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis
EP  - 66
IS  - 1-2
SP  - 55
VL  - 214
DO  - 10.1016/j.jneuroim.2009.06.018
ER  - 

@article{
author = "Pešić, Vesna and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Perišić, Milica and Vidić-Danković, Biljana and Leposavić, Gordana",
year = "2009",
abstract = "The study was undertaken to explore: i) the presence of alpha(1)-adrenoceptors (AR) on thymic lymphoid and non-lymphoid cells and ii) their putative role in T-cell development. The expression of alpha(1)-AR on thymic cells was assessed using both immunohistochemistry and flow cytometric analyses, while their putative role in thymopoiesis was estimated by analyses of thymocyte proliferation and apoptosis, and major thymocyte subset distribution in adult rats subjected to 14-day-long treatment with the alpha(1)-AR blocker urapidil. The presence of alpha(1)-AR was demonstrated on both thymocytes (mainly less mature CD3(-) and CD3(low) cells) and thymic non-lymphoid cells (thymic epithelial cells and CD68-positive cells). Chronic treatment with urapidil increased the thymic weight and thymocyte number. The increase in thymocyte number might, at least partly, be related to an enhanced thymocyte proliferation. In addition, an altered thymocyte subset distribution was observed in these rats. The increase in the percentage of CD4+CD8+ double positive (DP) TCR alpha beta(-) thymocytes was accompanied by the reduction in that of CD4+CD8+ (DP) TCR alpha beta(low) cells, and divergent changes in the percentage of the most mature single positive (SP) TCR alpha beta(high) high thymocytes. In urapidil-administered rats the percentage of CD4+CD8-SP TCR alpha beta(high) thymocytes was increased, while that of the CD4-CD8+ TCR alpha beta(high) was reduced. compared with controls. In addition, proportions of CD4+CD25+ RT6.1- and CD161+TCR alpha beta+ regulatory cells were increased. Collectively, the results indicate that alpha(1)-AR are involved in complex network of neuro-thymic and intrathymic communications that provide fine tuning of both conventional effector and regulatory T-cell development. (c) 2009 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis",
pages = "66-55",
number = "1-2",
volume = "214",
doi = "10.1016/j.jneuroim.2009.06.018"
}

Pešić, V., Kosec, D., Radojević, K., Pilipović, I., Perišić, M., Vidić-Danković, B.,& Leposavić, G.. (2009). Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis. in Journal of Neuroimmunology
Elsevier Science Bv, Amsterdam., 214(1-2), 55-66.
https://doi.org/10.1016/j.jneuroim.2009.06.018

Pešić V, Kosec D, Radojević K, Pilipović I, Perišić M, Vidić-Danković B, Leposavić G. Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis. in Journal of Neuroimmunology. 2009;214(1-2):55-66.
doi:10.1016/j.jneuroim.2009.06.018 .

Pešić, Vesna, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Perišić, Milica, Vidić-Danković, Biljana, Leposavić, Gordana, "Expression of alpha(1)-adrenoceptors on thymic cells and their role in fine tuning of thymopoiesis" in Journal of Neuroimmunology, 214, no. 1-2 (2009):55-66,
https://doi.org/10.1016/j.jneuroim.2009.06.018 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Pilipović, Ivan
AU  - Stanojević, Stanislava
AU  - Mitić, Katarina
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Leposavić, Gordana
PY  - 2009
UR  - http://intor.torlakinstitut.com/handle/123456789/273
AB  - Using both immunocytochemical and flow cytometric analyses of rat peritoneal exudate cells constitutive expression of tyrosine hydroxylase and both beta(2)- and alpha(1)-adrenoceptors on macrophages was revealed. Furthermore, according to the characteristic assemblage of tyrosine hydroxylase and adrenoceptor subtype expression different macrophage subsets were identified. In vitro treatment of macrophages with the nonselective alpha,beta-adrenoceptor agonist arterenol and/or the beta-adrenoceptor antagonist propranolol indicated that beta-adrenoceptors potentiated nitric oxide (NO) production and suggested alpha-adrenoceptor-mediated suppression of hydrogen peroxide (H2O2) production. An increase in H2O2 production in the presence of the alpha(1)-adrenoceptor antagonist ebrantil provided support for this. Chronic propranolol treatment in vivo led to increased NO and H2O2 production by peritoneal macrophages. Furthermore, this treatment resulted in opposing effects on the expression Of beta(2)- and alpha(1)-adrenoceptors on peritoneal macrophages (a stimulatory effect on beta(2)-adrenoceptors and a suppressive effect on alpha(1)-adrenoceptors). In conclusion, a subset of resident peritoneal macrophages synthesizes catecholamines, which may exert differential effects on H2O2 and NO production via distinct adrenoceptors. Finally, chronic propranolol treatment affected adrenoceptor expression on peritoneal macrophages and altered their capacity to generate NO and H2O2. (C) 2009 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide
EP  - 65
IS  - 1-2
SP  - 56
VL  - 211
DO  - 10.1016/j.jneuroim.2009.03.014
ER  - 

@article{
author = "Dimitrijević, Mirjana and Pilipović, Ivan and Stanojević, Stanislava and Mitić, Katarina and Radojević, Katarina and Pešić, Vesna and Leposavić, Gordana",
year = "2009",
abstract = "Using both immunocytochemical and flow cytometric analyses of rat peritoneal exudate cells constitutive expression of tyrosine hydroxylase and both beta(2)- and alpha(1)-adrenoceptors on macrophages was revealed. Furthermore, according to the characteristic assemblage of tyrosine hydroxylase and adrenoceptor subtype expression different macrophage subsets were identified. In vitro treatment of macrophages with the nonselective alpha,beta-adrenoceptor agonist arterenol and/or the beta-adrenoceptor antagonist propranolol indicated that beta-adrenoceptors potentiated nitric oxide (NO) production and suggested alpha-adrenoceptor-mediated suppression of hydrogen peroxide (H2O2) production. An increase in H2O2 production in the presence of the alpha(1)-adrenoceptor antagonist ebrantil provided support for this. Chronic propranolol treatment in vivo led to increased NO and H2O2 production by peritoneal macrophages. Furthermore, this treatment resulted in opposing effects on the expression Of beta(2)- and alpha(1)-adrenoceptors on peritoneal macrophages (a stimulatory effect on beta(2)-adrenoceptors and a suppressive effect on alpha(1)-adrenoceptors). In conclusion, a subset of resident peritoneal macrophages synthesizes catecholamines, which may exert differential effects on H2O2 and NO production via distinct adrenoceptors. Finally, chronic propranolol treatment affected adrenoceptor expression on peritoneal macrophages and altered their capacity to generate NO and H2O2. (C) 2009 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide",
pages = "65-56",
number = "1-2",
volume = "211",
doi = "10.1016/j.jneuroim.2009.03.014"
}

Dimitrijević, M., Pilipović, I., Stanojević, S., Mitić, K., Radojević, K., Pešić, V.,& Leposavić, G.. (2009). Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide. in Journal of Neuroimmunology
Elsevier, Amsterdam., 211(1-2), 56-65.
https://doi.org/10.1016/j.jneuroim.2009.03.014

Dimitrijević M, Pilipović I, Stanojević S, Mitić K, Radojević K, Pešić V, Leposavić G. Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide. in Journal of Neuroimmunology. 2009;211(1-2):56-65.
doi:10.1016/j.jneuroim.2009.03.014 .

Dimitrijević, Mirjana, Pilipović, Ivan, Stanojević, Stanislava, Mitić, Katarina, Radojević, Katarina, Pešić, Vesna, Leposavić, Gordana, "Chronic propranolol treatment affects expression of adrenoceptors on peritoneal macrophages and their ability to produce hydrogen peroxide and nitric oxide" in Journal of Neuroimmunology, 211, no. 1-2 (2009):56-65,
https://doi.org/10.1016/j.jneuroim.2009.03.014 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Radojević, Katarina
AU  - Pešić, Vesna
AU  - Perišić, Milica
AU  - Kosec, Duško
PY  - 2008
UR  - http://intor.torlakinstitut.com/handle/123456789/244
AB  - In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated tit response to antigen. In establishing and maintaining the peripheral T-cell pool, the thymus plays a critical role. It does so by providing a microenvironment within which T cell precursors proliferate, differentiate and Undergo selection processes to create a fully functional population of major histocompatibility complex restricted, self-tolerant T cells. The control of the thymic function involves intrathymic, as well as sympathetic nervous and endocrine system signalling. In addition to postganglionic noradrenergic fibres, both thymic lymphoid and non-lymphoid cells, including epithelial cells and macrophages. have been demo nstrated to express tyrosine hydroxylase (TH), and Suggested to form a local non-neural catecholaminergic cell network. A higher level of noradrenaline has been found in male than in female rat thymi. and a role of,gonadal hormones ill providing this dimorphism has been demonstrated. In addition, thymic lymphoid and non-lymphoid cells, including those expressing TH, have been found to bear beta- and alpha(1)-adrenoceptors (ARs) and a role of gonadal hormones in regulation of, at least. beta-AR density and signalling has been Suggested. These findings have also entailed conclusion that catecholamiens (CAs) influence T-cell development, not only via neurocrine/endocrine, but also via autocrine/paracrine action. Generally, CAs have been shown to exert an inhibitory influence on thymopoiesis. Role of alpha(1)- and beta-R-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the Manuscript. (C) 2008 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Autonomic Neuroscience-Basic & Clinical
T1  - Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development
EP  - 12
IS  - 1-2
SP  - 1
VL  - 144
DO  - 10.1016/j.autneu.2008.09.003
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Radojević, Katarina and Pešić, Vesna and Perišić, Milica and Kosec, Duško",
year = "2008",
abstract = "In its simplest form, effective T cell-mediated immunity emanates from the expansion of specific T cells activated tit response to antigen. In establishing and maintaining the peripheral T-cell pool, the thymus plays a critical role. It does so by providing a microenvironment within which T cell precursors proliferate, differentiate and Undergo selection processes to create a fully functional population of major histocompatibility complex restricted, self-tolerant T cells. The control of the thymic function involves intrathymic, as well as sympathetic nervous and endocrine system signalling. In addition to postganglionic noradrenergic fibres, both thymic lymphoid and non-lymphoid cells, including epithelial cells and macrophages. have been demo nstrated to express tyrosine hydroxylase (TH), and Suggested to form a local non-neural catecholaminergic cell network. A higher level of noradrenaline has been found in male than in female rat thymi. and a role of,gonadal hormones ill providing this dimorphism has been demonstrated. In addition, thymic lymphoid and non-lymphoid cells, including those expressing TH, have been found to bear beta- and alpha(1)-adrenoceptors (ARs) and a role of gonadal hormones in regulation of, at least. beta-AR density and signalling has been Suggested. These findings have also entailed conclusion that catecholamiens (CAs) influence T-cell development, not only via neurocrine/endocrine, but also via autocrine/paracrine action. Generally, CAs have been shown to exert an inhibitory influence on thymopoiesis. Role of alpha(1)- and beta-R-mediated mechanisms in maintaining thymic homeostasis and in fine tuning of both conventional and regulatory T-cell development is discussed in the Manuscript. (C) 2008 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Autonomic Neuroscience-Basic & Clinical",
title = "Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development",
pages = "12-1",
number = "1-2",
volume = "144",
doi = "10.1016/j.autneu.2008.09.003"
}

Leposavić, G., Pilipović, I., Radojević, K., Pešić, V., Perišić, M.,& Kosec, D.. (2008). Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development. in Autonomic Neuroscience-Basic & Clinical
Elsevier Science Bv, Amsterdam., 144(1-2), 1-12.
https://doi.org/10.1016/j.autneu.2008.09.003

Leposavić G, Pilipović I, Radojević K, Pešić V, Perišić M, Kosec D. Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development. in Autonomic Neuroscience-Basic & Clinical. 2008;144(1-2):1-12.
doi:10.1016/j.autneu.2008.09.003 .

Leposavić, Gordana, Pilipović, Ivan, Radojević, Katarina, Pešić, Vesna, Perišić, Milica, Kosec, Duško, "Catecholamines as immunomodulators: A role for adrenoceptor-mediated mechanisms in fine tuning of T-cell development" in Autonomic Neuroscience-Basic & Clinical, 144, no. 1-2 (2008):1-12,
https://doi.org/10.1016/j.autneu.2008.09.003 . .

TY  - JOUR
AU  - Pilipović, Ivan
AU  - Vidić-Danković, Biljana
AU  - Perišić, Milica
AU  - Radojević, Katarina
AU  - Colić, Miodrag
AU  - Todorović, Vera
AU  - Leposavić, Gordana
PY  - 2008
UR  - http://intor.torlakinstitut.com/handle/123456789/250
AB  - The study was undertaken to explore whether there were: i) apart from neural and circulatory, some other sources of catecholamines (CAs) in rat thymus and ii) gender-specific differences in thymic CA levels, and if so to elucidate the role of sex steroids in this phenomenon. Tyrosine hydroxylase (TH) immunoreactivity was found in thymocytes and thymic epithelial cells (some of which showed morphological features of nurse cells). The density of CA-synthesizing cells was greater in male than in female rats. Noradrenaline (NA), but not dopamine (DA), was detected in thymocytes. NA and DA levels in thymi, and the NA level in thymocytes, were higher in male rats. To explore the Putative role of sex steroids in this dichotomy in the thymi of adult rats gonadectomized (Gx) or sham-Gx at the age of 30 days the density of TH+ cells and CA levels were measured. Gonadectomy abolished sexual dimorphism in the density of thymic TH+ cells (diminishing their density in male rats) and thymic CA levels (the NA levels were reduced in rats of both sexes and also the DA level in male rats). Therefore, it can be assumed that testicular and ovarian hormones control thymic NA and DA levels via different mechanisms. Moreover, in Gx rats, despite the decrease in the overall thymic NA level, an increase in the thymocyte NA level was found indicating that gonadal hormones exert differential effects on the NA level in distinct thymic cellular compartments. (C) 2007 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones
EP  - 20
IS  - 1-2
SP  - 7
VL  - 195
DO  - 10.1016/j.jneuroim.2007.12.006
ER  - 

@article{
author = "Pilipović, Ivan and Vidić-Danković, Biljana and Perišić, Milica and Radojević, Katarina and Colić, Miodrag and Todorović, Vera and Leposavić, Gordana",
year = "2008",
abstract = "The study was undertaken to explore whether there were: i) apart from neural and circulatory, some other sources of catecholamines (CAs) in rat thymus and ii) gender-specific differences in thymic CA levels, and if so to elucidate the role of sex steroids in this phenomenon. Tyrosine hydroxylase (TH) immunoreactivity was found in thymocytes and thymic epithelial cells (some of which showed morphological features of nurse cells). The density of CA-synthesizing cells was greater in male than in female rats. Noradrenaline (NA), but not dopamine (DA), was detected in thymocytes. NA and DA levels in thymi, and the NA level in thymocytes, were higher in male rats. To explore the Putative role of sex steroids in this dichotomy in the thymi of adult rats gonadectomized (Gx) or sham-Gx at the age of 30 days the density of TH+ cells and CA levels were measured. Gonadectomy abolished sexual dimorphism in the density of thymic TH+ cells (diminishing their density in male rats) and thymic CA levels (the NA levels were reduced in rats of both sexes and also the DA level in male rats). Therefore, it can be assumed that testicular and ovarian hormones control thymic NA and DA levels via different mechanisms. Moreover, in Gx rats, despite the decrease in the overall thymic NA level, an increase in the thymocyte NA level was found indicating that gonadal hormones exert differential effects on the NA level in distinct thymic cellular compartments. (C) 2007 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones",
pages = "20-7",
number = "1-2",
volume = "195",
doi = "10.1016/j.jneuroim.2007.12.006"
}

Pilipović, I., Vidić-Danković, B., Perišić, M., Radojević, K., Colić, M., Todorović, V.,& Leposavić, G.. (2008). Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones. in Journal of Neuroimmunology
Elsevier Science Bv, Amsterdam., 195(1-2), 7-20.
https://doi.org/10.1016/j.jneuroim.2007.12.006

Pilipović I, Vidić-Danković B, Perišić M, Radojević K, Colić M, Todorović V, Leposavić G. Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones. in Journal of Neuroimmunology. 2008;195(1-2):7-20.
doi:10.1016/j.jneuroim.2007.12.006 .

Pilipović, Ivan, Vidić-Danković, Biljana, Perišić, Milica, Radojević, Katarina, Colić, Miodrag, Todorović, Vera, Leposavić, Gordana, "Sexual dimorphism in the catecholamine-containing thymus microenvironment: A role for gonadal hormones" in Journal of Neuroimmunology, 195, no. 1-2 (2008):7-20,
https://doi.org/10.1016/j.jneuroim.2007.12.006 . .

TY  - JOUR
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pešić, Vesna
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2007
UR  - http://intor.torlakinstitut.com/handle/123456789/240
AB  - To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.
PB  - Bioscientifica Ltd, Bristol
T2  - Journal of Endocrinology
T1  - Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level
EP  - 682
IS  - 3
SP  - 669
VL  - 192
DO  - 10.1677/joe.1.07019
ER  - 

@article{
author = "Radojević, Katarina and Arsenović-Ranin, Nevena and Kosec, Duško and Pešić, Vesna and Pilipović, Ivan and Perišić, Milica and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2007",
abstract = "To test putative interdependence in the ontogenesis of the hypothalamic-pituitary-gonadal and thymic-lymphatic axes, thymocyte differentiation and maturation was examined in neonatally castrated (Cx) adult rats. In the hypercellular thymi of Cx rats, the proportion of the least mature CD4(-)CD8(-)TCR alpha beta(-) triple negative (TN) thymocytes was reduced, while the proportions of all downstream double positive (DP) subsets (TCR alpha beta(-), TCR alpha beta(low) and TCR alpha beta(high)) were increased when compared with neonatally sham-castrated (Sx) adult rats. This suggested an accelerated thymocyte transition from the TN to DP TCR alpha beta(low) developmental stage accompanied by an increased positive/reduced negative thymocyte selection. The increased thymocyte surface density of Thy-1, which is implicated in thymocyte hyposensitivity to negative selection, in Cx rats further supports the previous assumption. The finding that the proportions of both single positive (SP) TCR alpha beta(high) thymocyte subsets were reduced, while their numbers were increased (CD4(+)CD8(-)) or unaltered (CD4(-)CD8(+)), coupled with results demonstrating an increased level of CD4(-)CD8(+) cells without changes in that of CD4(+) 8(-) cells in the spleen indicate: (i) accelerated differentiation and maturation of the positively selected DP TCR alpha beta(high) thymocytes towards CD4(-)8(+) TCR alpha beta(high) cells followed by increased emigration of the mature cells and (ii) decelerated hi h differentiation and maturation towards CD4(+)8(-) TCR alpha beta(high) cells in Cx rats. Furthermore, the unaltered proportion of intrathymically developing CD4(+)CD25(+)Foxp3(+) regulatory cells in Cx rats, in light of putative hyposensitivity of thymocytes to negative selection suggesting reduced elimination of autoreactive cells, may provide a firm basis for understanding the reasons behind increased susceptibility of Cx rats to autoimmune disease induction.",
publisher = "Bioscientifica Ltd, Bristol",
journal = "Journal of Endocrinology",
title = "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level",
pages = "682-669",
number = "3",
volume = "192",
doi = "10.1677/joe.1.07019"
}

Radojević, K., Arsenović-Ranin, N., Kosec, D., Pešić, V., Pilipović, I., Perišić, M., Plećaš-Solarović, B.,& Leposavić, G.. (2007). Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology
Bioscientifica Ltd, Bristol., 192(3), 669-682.
https://doi.org/10.1677/joe.1.07019

Radojević K, Arsenović-Ranin N, Kosec D, Pešić V, Pilipović I, Perišić M, Plećaš-Solarović B, Leposavić G. Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level. in Journal of Endocrinology. 2007;192(3):669-682.
doi:10.1677/joe.1.07019 .

Radojević, Katarina, Arsenović-Ranin, Nevena, Kosec, Duško, Pešić, Vesna, Pilipović, Ivan, Perišić, Milica, Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Neonatal castration affects intrathymic kinetics of T-cell differentiation and the spleen T-cell level" in Journal of Endocrinology, 192, no. 3 (2007):669-682,
https://doi.org/10.1677/joe.1.07019 . .

TY  - JOUR
AU  - Pešić, Vesna
AU  - Plećaš-Solarović, Bosiljka
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Leposavić, Gordana
PY  - 2007
UR  - http://intor.torlakinstitut.com/handle/123456789/239
AB  - Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P. (c) 2007 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - International Immunopharmacology
T1  - Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats
EP  - 686
IS  - 5
SP  - 674
VL  - 7
DO  - 10.1016/j.intimp.2007.01.017
ER  - 

@article{
author = "Pešić, Vesna and Plećaš-Solarović, Bosiljka and Radojević, Katarina and Kosec, Duško and Pilipović, Ivan and Perišić, Milica and Leposavić, Gordana",
year = "2007",
abstract = "Age-related increase in the density of thymic noradrenergic fibres and noradrenaline (NA) concentration is proposed to be associated with thymic involution and altered thymopoiesis. To test this hypothesis thymocyte differentiation/maturation and thymic structure were studied in 18-month-old male Wistar rats subjected to 14-day-long propranolol (P) blockade of ss-adrenoceptors (ss-ARs). The treatment primarily resulted in changes in the T-cell receptor (TCR)-dependent stages of thymopoiesis, which led to an increase in both the relative and absolute numbers of the most mature single positive (SP) CD4(+)CD8(-) (including cells with the CD4(+)CD25(+) regulatory phenotype) and CD4(-)CD8(+) TCR alpha ss(high) thymocytes. Accordingly, in the thymi of these rats an increase in both numerical density and absolute number of medullary thymocytes encompassing mainly the most mature SP cells was found. These findings, together with an increase in the thymocyte surface expression of the regulatory molecule Thy-1 (CD90) (implicated in negative regulation of TCR alpha beta-dependent thymocyte selection thresholds) in the same rats, may suggest increased positive/reduced negative thymocyte selection. Collectively, the results indicate that a decline in thymic efficiency in generating both conventional and regulatory T cells, and consequently in immune function, in aged rats may be, at least partly, attenuated by long-term blockade of beta-ARs with P. (c) 2007 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "International Immunopharmacology",
title = "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats",
pages = "686-674",
number = "5",
volume = "7",
doi = "10.1016/j.intimp.2007.01.017"
}

Pešić, V., Plećaš-Solarović, B., Radojević, K., Kosec, D., Pilipović, I., Perišić, M.,& Leposavić, G.. (2007). Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology
Elsevier, Amsterdam., 7(5), 674-686.
https://doi.org/10.1016/j.intimp.2007.01.017

Pešić V, Plećaš-Solarović B, Radojević K, Kosec D, Pilipović I, Perišić M, Leposavić G. Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats. in International Immunopharmacology. 2007;7(5):674-686.
doi:10.1016/j.intimp.2007.01.017 .

Pešić, Vesna, Plećaš-Solarović, Bosiljka, Radojević, Katarina, Kosec, Duško, Pilipović, Ivan, Perišić, Milica, Leposavić, Gordana, "Long-term beta-adrenergic receptor blockade increases levels of the most mature thymocyte subsets in aged rats" in International Immunopharmacology, 7, no. 5 (2007):674-686,
https://doi.org/10.1016/j.intimp.2007.01.017 . .

TY  - JOUR
AU  - Pešić, Vesna
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Plećaš-Solarović, Bosiljka
AU  - Perišić, Milica
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - http://intor.torlakinstitut.com/handle/123456789/232
AB  - The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.
PB  - Assoc Bras Divulg Cientifica, Sao Paulo
T2  - Brazilian Journal of Medical and Biological Research
T1  - Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats
EP  - 1493
IS  - 11
SP  - 1481
VL  - 40
DO  - 10.1590/S0100-879X2006005000172
ER  - 

@article{
author = "Pešić, Vesna and Radojević, Katarina and Kosec, Duško and Plećaš-Solarović, Bosiljka and Perišić, Milica and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "The role of gonadal hormones in induction and, particularly, maintenance/ progression of rat thymic involution, which normally starts around puberty, was reassessed by examining the effects of peripubertal orchidectomy on thymic weight and morphometric parameters at different times up to the age of 10 months. Up to 6 months post-castration both thymic weight and cellularity in orchidectomized ( Cx) rats were greater than in age-matched control rats, sham Cx ( Sx). The increase in thymic cellularity reflected an increase in thymocyte proliferation rate ( the proportion of proliferating cells was 18.6 +/- 0.7% in 2-month-old Cx ( N = 5) vs 13.4 +/- 0.3% ( N = 5) in age-matched Sx rats) followed by reduced sensitivity to apoptotic signals ( apoptotic thymocytes were 9.8 +/- 0.9% in 2-month-old Cx ( N = 5) vs 15.5 +/- 0.3% ( N = 5) age-matched Sx rats). However, 9 months post-orchidectomy, neither thymic weight and cellularity nor any of the morphometric parameters analyzed differed between Cx and control rats. The reduction of thymic cellularity in Cx rats to control values may be related to increased sensitivity of their thymocytes to apoptotic signals in culture ( 72.6 +/- 1.2% in 10-month-old vs 9.8 +/- 0.9% in 2-month-old Cx rats) followed by reduced responsiveness to proliferative stimuli ( 14.1 +/- 0.2% in 10-month-old vs 18.6 +/- 0.7% in 2-month-old Cx rats). Thus, the study indicates that the effects of peripubertal orchidectomy on thymic weight and cellularity, as well as on the main morphometric indices, are long-lasting but not permanent, i.e., that removal of the testes can only postpone but not prevent age-related organ atrophy and consequently functional deterioration of the immune system.",
publisher = "Assoc Bras Divulg Cientifica, Sao Paulo",
journal = "Brazilian Journal of Medical and Biological Research",
title = "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats",
pages = "1493-1481",
number = "11",
volume = "40",
doi = "10.1590/S0100-879X2006005000172"
}

Pešić, V., Radojević, K., Kosec, D., Plećaš-Solarović, B., Perišić, M., Pilipović, I.,& Leposavić, G.. (2007). Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research
Assoc Bras Divulg Cientifica, Sao Paulo., 40(11), 1481-1493.
https://doi.org/10.1590/S0100-879X2006005000172

Pešić V, Radojević K, Kosec D, Plećaš-Solarović B, Perišić M, Pilipović I, Leposavić G. Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats. in Brazilian Journal of Medical and Biological Research. 2007;40(11):1481-1493.
doi:10.1590/S0100-879X2006005000172 .

Pešić, Vesna, Radojević, Katarina, Kosec, Duško, Plećaš-Solarović, Bosiljka, Perišić, Milica, Pilipović, Ivan, Leposavić, Gordana, "Peripubertal orchidectomy transitorily affects age-associated thymic involution in rats" in Brazilian Journal of Medical and Biological Research, 40, no. 11 (2007):1481-1493,
https://doi.org/10.1590/S0100-879X2006005000172 . .

TY  - JOUR
AU  - Dimitrijević, Mirjana
AU  - Rauški, Aleksandra
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Stanojević, Stanislava
AU  - Pilipović, Ivan
AU  - Leposavić, Gordana
PY  - 2007
UR  - http://intor.torlakinstitut.com/handle/123456789/230
AB  - As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease. (c) 2007 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - European Journal of Pharmacology
T1  - Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats
EP  - 182
IS  - 1-3
SP  - 170
VL  - 577
DO  - 10.1016/j.ejphar.2007.08.021
ER  - 

@article{
author = "Dimitrijević, Mirjana and Rauški, Aleksandra and Radojević, Katarina and Kosec, Duško and Stanojević, Stanislava and Pilipović, Ivan and Leposavić, Gordana",
year = "2007",
abstract = "As glucocorticoids influence both catecholamine synthesis and adrenoceptor expression by immune cells, the current study was undertaken to distinguish their direct effects on the development of experimental allergic encephalomyelitis from those induced by alteration of catecholamine signaling. We examined the influence of 16-day-long beta-adrenoceptor blockade with propranolol (0.40 mg/100 g body weight/day, s.c.) beginning 3 days before immunization on the development of experimental allergic encephalomyelitis in adrenalectomized (7 days before immunization) and in non-operated male Dark Agouti rats. Adrenalectomy aggravated the clinical course of experimental allergic encephalomyelitis. In contrast, propranolol attenuated both the clinical signs of the disease and decreased the number of lesions in the spinal cord. Furthermore, propranolol prevented adrenalectomy-induced aggravation of the disease course without affecting mortality. We also found that the percentage of CD4(+)CD25(+) T lymphocytes (recently activated or regulatory cells) was increased in peripheral blood of experimental allergic encephalomyelitis rats over that in the corresponding non-immunized and bovine serum albumin immunized rats. However, the percentage of these cells was reduced in adrenalectomized and/or propranolol-treated experimental allergic encephalomyelitis rats compared to control experimental allergic encephalomyelitis rats. Our findings, coupled with the clinical course of the disease and the underlying pathomorphological changes, clearly suggest that differential mechanisms were responsible for the changes in the percentage of CD4(+)CD25(+) T lymphocytes in propranolol-treated adrenalectomized rats and only propranolol-treated rats with experimental allergic encephalomyelitis. Our results, when viewed globally, indicate that: i) beta-adrenoceptor-dependent mechanisms are involved in the immunopathogenesis of experimental allergic encephalomyelitis, ii) experimental allergic encephalomyelitis has a more severe course in adrenalectomized rats and iii) beta-adrenoceptor-mediated mechanisms operate in adrenalectomy-induced aggravation of the disease. (c) 2007 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "European Journal of Pharmacology",
title = "Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats",
pages = "182-170",
number = "1-3",
volume = "577",
doi = "10.1016/j.ejphar.2007.08.021"
}

Dimitrijević, M., Rauški, A., Radojević, K., Kosec, D., Stanojević, S., Pilipović, I.,& Leposavić, G.. (2007). Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology
Elsevier Science Bv, Amsterdam., 577(1-3), 170-182.
https://doi.org/10.1016/j.ejphar.2007.08.021

Dimitrijević M, Rauški A, Radojević K, Kosec D, Stanojević S, Pilipović I, Leposavić G. Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats. in European Journal of Pharmacology. 2007;577(1-3):170-182.
doi:10.1016/j.ejphar.2007.08.021 .

Dimitrijević, Mirjana, Rauški, Aleksandra, Radojević, Katarina, Kosec, Duško, Stanojević, Stanislava, Pilipović, Ivan, Leposavić, Gordana, "Beta-adrenoceptor blockade ameliorates the clinical course of experimental allergic encephalomyelitis and diminishes its aggravation in adrenalectomized rats" in European Journal of Pharmacology, 577, no. 1-3 (2007):170-182,
https://doi.org/10.1016/j.ejphar.2007.08.021 . .