TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Đikić, Jasmina
AU  - Vujnović, Ivana
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2018
UR  - http://intor.torlakinstitut.com/handle/123456789/516
AB  - The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis
EP  - 53
SP  - 37
VL  - 101
DO  - 10.1016/j.exger.2017.11.002
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Pilipović, Ivan and Đikić, Jasmina and Vujnović, Ivana and Nacka-Aleksić, Mirjana and Bufan, Biljana and Arsenović-Ranin, Nevena and Kosec, Duško and Leposavić, Gordana",
year = "2018",
abstract = "The study investigated strain specificities in age-related differences in CD8+ T cell-and microglial cell-mediated mechanisms implicated in induction/perpetuation and/or control of neuroinflammation in experimental autoimmune encephalomyelitis (EAE) in Albino Oxford (AO) and Dark Agouti (DA) rats exhibiting age-related changes in the susceptibility to EAE in the opposite direction (increase in relatively resistant AO rats vs decrease in DA rats). In the inductive phase of EAE, the greater number of fully differentiated effector CD8+ T lymphocytes was found in draining lymph nodes (dLNs) from aged rats of both strains than in strain-matched young rats, but this was particularly prominent in AO rats, which exhibited milder EAE of prolonged duration compared with their DA counterparts. Consistently, dLN IFN-gamma+ and IL-17+ CD8+ T cell counts were greater in aged AO than in DA rats. Additionally, the magnitudes of myelin basic protein (MBP)-induced rise in the frequency of IFN-gamma+ and IL-17+ CD8+ T cells (providing important help to neuroantigen-specific CD4+ T cells in EAE models characterized by clinically mild disease) were greater in dLN cell cultures from aged AO rats. Consistently, the magnitudes of MBP-induced rise in the frequency of both IFN-gamma+ and IL-17+ CD8+ T cells were greater in spinal cord mononuclear cell cultures from aged AO rats compared with their DA counterparts. Besides, with aging CD4+ CD25+ Foxp3+/CD8+ CD25+ Foxp3+ regulatory T cell ratio changed in spinal cord in the opposite direction. Consequently, in aged AO rats it was shifted towards CD8+ CD25+ Foxp3+ regulatory T cells (exhibiting lower suppressive capacity) when compared with DA rats. Moreover, the frequency of CX3CR1+ cells among microglia changed with aging and the disease development. In aged rats, in the effector phase of EAE it was lower in AO than in DA rats. This was accompanied by higher frequency of cells expressing IL-1 beta (whose down-regulation is central for CX3CR1-mediated neuroprotection), but lower that of phagocyting cells among microglia from aged AO compared their DA counterparts. The study indicates the control points linked with strain differences in age-related changes in EAE pathogenesis.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis",
pages = "53-37",
volume = "101",
doi = "10.1016/j.exger.2017.11.002"
}

Stojić-Vukanić, Z., Pilipović, I., Đikić, J., Vujnović, I., Nacka-Aleksić, M., Bufan, B., Arsenović-Ranin, N., Kosec, D.,& Leposavić, G.. (2018). Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 101, 37-53.
https://doi.org/10.1016/j.exger.2017.11.002

Stojić-Vukanić Z, Pilipović I, Đikić J, Vujnović I, Nacka-Aleksić M, Bufan B, Arsenović-Ranin N, Kosec D, Leposavić G. Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis. in Experimental Gerontology. 2018;101:37-53.
doi:10.1016/j.exger.2017.11.002 .

Stojić-Vukanić, Zorica, Pilipović, Ivan, Đikić, Jasmina, Vujnović, Ivana, Nacka-Aleksić, Mirjana, Bufan, Biljana, Arsenović-Ranin, Nevena, Kosec, Duško, Leposavić, Gordana, "Strain specificities in age-related changes in mechanisms promoting and controlling rat spinal cord damage in experimental autoimmune encephalomyelitis" in Experimental Gerontology, 101 (2018):37-53,
https://doi.org/10.1016/j.exger.2017.11.002 . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Đikić, Jasmina
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Nacka-Aleksić, Mirjana
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/448
AB  - The study was undertaken considering: i) that relative proportion of distinct subsets of splenic dendritic cells (DCs) is strain-specific and predictive for the susceptibility to autoimmune diseases; ii) age-related changes in endocytic, allostimulatory and polarizing capacity of splenic OX62+ DCs from Albino Oxford rats (relatively resistant to Th1/Th17-mediated diseases) and iii) strain specificities in age-related changes of mouse DCs. To ascertain whether there are strain specificities in age-related rat DC changes, we examined the influence of aging on OX62+ DCs from Dark Agouti (DA) rats prone to Th1/Th17-mediated autoimmune diseases. The study provided additional evidence that the predominance of CD4-cells within OX62+ DCs from young adult rats correlates with their susceptibility to Th1/Th17-mediated diseases. Consistently, lipopolysaccharide (LPS)-matured DCs from 3-month-old (young) rats exhibited Th1 driving force when co-cultured with allogeneic CD4+ T cells. This most likely reflected enhanced TNF-alpha and iNOS expression. Comparing with young rats, OX62+ DCs from 26-month-old (aged) rats showed: i) diminished endocytic capacity; ii) impaired ability to mature in vitro upon LPS stimulation (as indicated by lower MHC II, CD86 and CD40 surface expression), which is consistent with the increase in their IL-10 production, and iii) diminished allostimulatory capacity and loss of Th1-driving capacity in the mixed lymphocyte reaction. The latter, probably, reflected greater IL-10 production by LPS-stimulated DC from aged rats, as well as lower CD40 density on their surface. Overall, our findings suggest that aging might affect DA rat capability to mount an efficient Th1 immune response, and consequently susceptibility to Th1/Th17-mediated pathology.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria - Beograd
T1  - Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation
EP  - 55
IS  - 1
SP  - 30
VL  - 65
DO  - 10.1515/acve-2015-0003
ER  - 

@article{
author = "Bufan, Biljana and Stojić-Vukanić, Zorica and Đikić, Jasmina and Kosec, Duško and Pilipović, Ivan and Nacka-Aleksić, Mirjana and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2015",
abstract = "The study was undertaken considering: i) that relative proportion of distinct subsets of splenic dendritic cells (DCs) is strain-specific and predictive for the susceptibility to autoimmune diseases; ii) age-related changes in endocytic, allostimulatory and polarizing capacity of splenic OX62+ DCs from Albino Oxford rats (relatively resistant to Th1/Th17-mediated diseases) and iii) strain specificities in age-related changes of mouse DCs. To ascertain whether there are strain specificities in age-related rat DC changes, we examined the influence of aging on OX62+ DCs from Dark Agouti (DA) rats prone to Th1/Th17-mediated autoimmune diseases. The study provided additional evidence that the predominance of CD4-cells within OX62+ DCs from young adult rats correlates with their susceptibility to Th1/Th17-mediated diseases. Consistently, lipopolysaccharide (LPS)-matured DCs from 3-month-old (young) rats exhibited Th1 driving force when co-cultured with allogeneic CD4+ T cells. This most likely reflected enhanced TNF-alpha and iNOS expression. Comparing with young rats, OX62+ DCs from 26-month-old (aged) rats showed: i) diminished endocytic capacity; ii) impaired ability to mature in vitro upon LPS stimulation (as indicated by lower MHC II, CD86 and CD40 surface expression), which is consistent with the increase in their IL-10 production, and iii) diminished allostimulatory capacity and loss of Th1-driving capacity in the mixed lymphocyte reaction. The latter, probably, reflected greater IL-10 production by LPS-stimulated DC from aged rats, as well as lower CD40 density on their surface. Overall, our findings suggest that aging might affect DA rat capability to mount an efficient Th1 immune response, and consequently susceptibility to Th1/Th17-mediated pathology.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria - Beograd",
title = "Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation",
pages = "55-30",
number = "1",
volume = "65",
doi = "10.1515/acve-2015-0003"
}

Bufan, B., Stojić-Vukanić, Z., Đikić, J., Kosec, D., Pilipović, I., Nacka-Aleksić, M., Arsenović-Ranin, N.,& Leposavić, G.. (2015). Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation. in Acta veterinaria - Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 65(1), 30-55.
https://doi.org/10.1515/acve-2015-0003

Bufan B, Stojić-Vukanić Z, Đikić J, Kosec D, Pilipović I, Nacka-Aleksić M, Arsenović-Ranin N, Leposavić G. Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation. in Acta veterinaria - Beograd. 2015;65(1):30-55.
doi:10.1515/acve-2015-0003 .

Bufan, Biljana, Stojić-Vukanić, Zorica, Đikić, Jasmina, Kosec, Duško, Pilipović, Ivan, Nacka-Aleksić, Mirjana, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Aging impairs endocytic capacity of splenic dendritic cells from dark agouti rats and alters their response to TLR4 stimulation" in Acta veterinaria - Beograd, 65, no. 1 (2015):30-55,
https://doi.org/10.1515/acve-2015-0003 . .

TY  - JOUR
AU  - Đikić, Jasmina
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/444
AB  - The study was undertaken considering age-related changes in susceptibility to experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in pathogenesis of this disease. The phenotypic and functional characteristics of T splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in complete Freund's adjuvant The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging. To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3 and CD4+CD40L+ cells, progressively increased with aging. This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3 + cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system. In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones. Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats. In addition, in control, as well as in ConA-and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-gamma concentrations were greater than in corresponding cultures from young rats. This most likely reflected increased abundance of IFN-gamma-producing cells in splenocyte cultures from aged compared with young rats. The diminished CD4+ cell proliferation in response to ConA and MBP in splenocyte cultures from aged compared with young rats could be, at least partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats. Thus, the study suggests that age-associated changes leading to entrapping of activated CD4+ cells in the spleen could contribute to the restriction in development of EAE in aged rats. (C) 2014 Elsevier B.V. All rights reserved.
PB  - Elsevier Science Bv, Amsterdam
T2  - Journal of Neuroimmunology
T1  - Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis
EP  - 135
SP  - 123
VL  - 278
DO  - 10.1016/j.jneuroim.2014.12.014
ER  - 

@article{
author = "Đikić, Jasmina and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Kosec, Duško and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2015",
abstract = "The study was undertaken considering age-related changes in susceptibility to experimental autoimmune encephalomyelitis (EAE) and a putative role of spleen in pathogenesis of this disease. The phenotypic and functional characteristics of T splenocytes were examined in young (3-month-old), middle-aged (8-month-old) and aged (26-month-old) Dark Agouti rats immunized for EAE with rat spinal cord in complete Freund's adjuvant The rat susceptibility to EAE induction, as well as the number of activated CD4+CD134+ lymphocytes retrieved from their spinal cords progressively decreased with aging. To the contrary, in rats immunized for EAE the number of activated CD4+ splenocytes, i.e., CD4+CD134+, CD4+CD25+FoxP3 and CD4+CD40L+ cells, progressively increased with aging. This was associated with age-related increase in (i) CD4+ splenocyte surface expression of CD44, the molecule suggested to be involved in limiting emigration of encephalitogenic CD4+ cells from spleen into blood and (ii) frequency of regulatory T cells, including CD4+CD25+FoxP3 + cells, which are also shown to control encephalitogenic cell migration from spleen into the central nervous system. In favor of expansion of T-regulatory cell pool in aged rats was the greater concentration of IL-10 in unstimulated, Concanavalin A (ConA)- and myelin basic protein (MBP)-stimulated splenocyte cultures from aged rats compared with the corresponding cultures from young ones. Consistent with the age-related increase in the expression of CD44, which is shown to favor Th1 effector cell survival by interfering with CD95-mediated signaling, the frequency of apoptotic cells among CD4+ splenocytes, despite the greater frequency of CD95+ cells, was diminished in splenocyte cultures from aged compared with young rats. In addition, in control, as well as in ConA-and MBP-stimulated splenocyte cultures from aged rats, despite of impaired CD4+ cell proliferation, IFN-gamma concentrations were greater than in corresponding cultures from young rats. This most likely reflected increased abundance of IFN-gamma-producing cells in splenocyte cultures from aged compared with young rats. The diminished CD4+ cell proliferation in response to ConA and MBP in splenocyte cultures from aged compared with young rats could be, at least partly, associated with an enhanced splenic expression of iNOS mRNA in aged rats. Thus, the study suggests that age-associated changes leading to entrapping of activated CD4+ cells in the spleen could contribute to the restriction in development of EAE in aged rats. (C) 2014 Elsevier B.V. All rights reserved.",
publisher = "Elsevier Science Bv, Amsterdam",
journal = "Journal of Neuroimmunology",
title = "Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis",
pages = "135-123",
volume = "278",
doi = "10.1016/j.jneuroim.2014.12.014"
}

Đikić, J., Nacka-Aleksić, M., Pilipović, I., Kosec, D., Arsenović-Ranin, N., Stojić-Vukanić, Z., Dimitrijević, M.,& Leposavić, G.. (2015). Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology
Elsevier Science Bv, Amsterdam., 278, 123-135.
https://doi.org/10.1016/j.jneuroim.2014.12.014

Đikić J, Nacka-Aleksić M, Pilipović I, Kosec D, Arsenović-Ranin N, Stojić-Vukanić Z, Dimitrijević M, Leposavić G. Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis. in Journal of Neuroimmunology. 2015;278:123-135.
doi:10.1016/j.jneuroim.2014.12.014 .

Đikić, Jasmina, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Kosec, Duško, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Leposavić, Gordana, "Age-related changes in spleen of Dark Agouti rats immunized for experimental autoimmune encephalomyelitis" in Journal of Neuroimmunology, 278 (2015):123-135,
https://doi.org/10.1016/j.jneuroim.2014.12.014 . .

TY  - JOUR
AU  - Stojić-Vukanić, Zorica
AU  - Nacka-Aleksić, Mirjana
AU  - Bufan, Biljana
AU  - Pilipović, Ivan
AU  - Arsenović-Ranin, Nevena
AU  - Đikić, Jasmina
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/442
AB  - This study was undertaken considering that, despite the broad use of the unopposed estrogen replacement therapy in elderly women, data on estrogen influence on the functional capacity of dendritic cells (DCs), and consequently immune response are limited. We examined the influence of 17 beta-estradiol on phenotype, cytokine secretory profile, and allostimulatory and polarizing capacity of splenic (OX62+) conventional DCs from 26-month-old (aged) Albino Oxford rats matured in vitro in the presence of LPS, a TLR4 agonist, and R848, a TLR7/8 agonist In the presence of 17 beta-estradiol, DCs from aged rats exhibited an impaired ability to mature upon stimulation with LPS, as shown by the lower surface density of MHC II and costimulatory CD80 and CD86 molecules. 17 beta-Estradiol alone enhanced CD40 expression in OX62+ DCs without affecting the expression of other costimulatory molecules, thereby confirming that the expression of this molecule is regulated independently from the regulation of other costimulatory molecules. However, although R848 upregulated the expression of MHC II and CD80 and CD40 costimulatory molecules on DCs, 17 beta-estradiol diminished the effect of this TLR agonist only on MHC II expression. In conjunction, the previous findings suggest that LPS and R848 elicit changes in the expression of costimulatory molecules via triggering differential intracellular signaling pathways. Furthermore, 17 beta-estradiol diminished the stimulatory influence of both LPS- and R848-matured OX62+ DCs on allogeneic CD4+ T lymphocyte proliferation in a mixed lymphocyte reaction (MLR). Moreover, as shown in MLR, the exposure to 17 beta-estradiol during LPS- and R848-induced maturation diminished Th1- and enhanced Th17-driving capacity and reduced Th1-driving capacity of OX62+ DCs, respectively. This suggests that LPS and R848 affect not only the surface phenotype, but also functional characteristics of OX62+ DCs triggering distinct intracellular signaling pathways. Collectively, the findings indicate that estrogen directly acting on OX62+ DCs, may affect CD4+ lymphocyte-dependent immune response in aged female rats. (C) 2014 Elsevier B.V. All rights reserved.
PB  - Elsevier, Amsterdam
T2  - International Immunopharmacology
T1  - 17 beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner
EP  - 35
IS  - 1
SP  - 24
VL  - 24
DO  - 10.1016/j.intimp.2014.11.008
ER  - 

@article{
author = "Stojić-Vukanić, Zorica and Nacka-Aleksić, Mirjana and Bufan, Biljana and Pilipović, Ivan and Arsenović-Ranin, Nevena and Đikić, Jasmina and Kosec, Duško and Leposavić, Gordana",
year = "2015",
abstract = "This study was undertaken considering that, despite the broad use of the unopposed estrogen replacement therapy in elderly women, data on estrogen influence on the functional capacity of dendritic cells (DCs), and consequently immune response are limited. We examined the influence of 17 beta-estradiol on phenotype, cytokine secretory profile, and allostimulatory and polarizing capacity of splenic (OX62+) conventional DCs from 26-month-old (aged) Albino Oxford rats matured in vitro in the presence of LPS, a TLR4 agonist, and R848, a TLR7/8 agonist In the presence of 17 beta-estradiol, DCs from aged rats exhibited an impaired ability to mature upon stimulation with LPS, as shown by the lower surface density of MHC II and costimulatory CD80 and CD86 molecules. 17 beta-Estradiol alone enhanced CD40 expression in OX62+ DCs without affecting the expression of other costimulatory molecules, thereby confirming that the expression of this molecule is regulated independently from the regulation of other costimulatory molecules. However, although R848 upregulated the expression of MHC II and CD80 and CD40 costimulatory molecules on DCs, 17 beta-estradiol diminished the effect of this TLR agonist only on MHC II expression. In conjunction, the previous findings suggest that LPS and R848 elicit changes in the expression of costimulatory molecules via triggering differential intracellular signaling pathways. Furthermore, 17 beta-estradiol diminished the stimulatory influence of both LPS- and R848-matured OX62+ DCs on allogeneic CD4+ T lymphocyte proliferation in a mixed lymphocyte reaction (MLR). Moreover, as shown in MLR, the exposure to 17 beta-estradiol during LPS- and R848-induced maturation diminished Th1- and enhanced Th17-driving capacity and reduced Th1-driving capacity of OX62+ DCs, respectively. This suggests that LPS and R848 affect not only the surface phenotype, but also functional characteristics of OX62+ DCs triggering distinct intracellular signaling pathways. Collectively, the findings indicate that estrogen directly acting on OX62+ DCs, may affect CD4+ lymphocyte-dependent immune response in aged female rats. (C) 2014 Elsevier B.V. All rights reserved.",
publisher = "Elsevier, Amsterdam",
journal = "International Immunopharmacology",
title = "17 beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner",
pages = "35-24",
number = "1",
volume = "24",
doi = "10.1016/j.intimp.2014.11.008"
}

Stojić-Vukanić, Z., Nacka-Aleksić, M., Bufan, B., Pilipović, I., Arsenović-Ranin, N., Đikić, J., Kosec, D.,& Leposavić, G.. (2015). 17 beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner. in International Immunopharmacology
Elsevier, Amsterdam., 24(1), 24-35.
https://doi.org/10.1016/j.intimp.2014.11.008

Stojić-Vukanić Z, Nacka-Aleksić M, Bufan B, Pilipović I, Arsenović-Ranin N, Đikić J, Kosec D, Leposavić G. 17 beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner. in International Immunopharmacology. 2015;24(1):24-35.
doi:10.1016/j.intimp.2014.11.008 .

Stojić-Vukanić, Zorica, Nacka-Aleksić, Mirjana, Bufan, Biljana, Pilipović, Ivan, Arsenović-Ranin, Nevena, Đikić, Jasmina, Kosec, Duško, Leposavić, Gordana, "17 beta-Estradiol influences in vitro response of aged rat splenic conventional dendritic cells to TLR4 and TLR7/8 agonists in an agonist specific manner" in International Immunopharmacology, 24, no. 1 (2015):24-35,
https://doi.org/10.1016/j.intimp.2014.11.008 . .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Đikić, Jasmina
AU  - Bufan, Biljana
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/429
AB  - The study examined the putative role of ovarian hormones in shaping of rat peripheral T-cell compartment during post-reproductive period. In 20-month-old rats ovariectomized (Ox) at the very end of reproductive period, thymic output, cellularity and composition of major TCR alpha beta+peripheral blood lymphocyte and splenocyte subsets were analyzed. Ovariectomy led to the enlargement of CD8 + peripheral blood lymphocyte and splenocyte subpopulations. This reflected: (i) a more efficient thymic generation of CD8 + cells as indicated by increased number of CD4+CD8+double positive and the most mature CD4CD8+TCR alpha beta(high) thymocytes and CD8 + recent thymic emigrants (RTEs) in peripheral blood, but not in the spleen of Ox rats, and (ii) the expansion of CD8 + memory/activated peripheral blood lymphocytes and splenocytes. The latter was consistent with a greater frequency of proliferating cells among freshly isolated memory/activated CD8 + peripheral blood lymphocytes and splenocytes and increased proliferative response of CD8 + splenocytes to stimulation with plate-bound anti-CD3 antibody. The former could be related to the rise in splenic IL-7 and IL-15 mRNA expression. Although ovariectomy affected the overall number of CD4 + T cells in none of the examined compartments, it increased CD4+FoxP3 + peripheral blood lymphocyte and splenocyte counts by enhancing their generation in periphery. Collectively, the results suggest that ovariectomy-induced long-lasting disturbances in ovarian hormone levels (mirrored in diminished progesterone serum level in 20-month-old rats) affects both thymic CD8 + cell generation and peripheral homeostasis and leads to the expansion of CD4+FoxP3 + cells in the periphery, thereby enhancing autoreactive cell control on account of immune system efficacy to combat infections and tumors.
PB  - Sage Publications Ltd, London
T2  - Experimental Biology and Medicine
T1  - Ovarian hormone level alterations during rat post-reproductive life-span influence CD8+T-cell homeostasis
EP  - 1332
IS  - 10
SP  - 1319
VL  - 240
DO  - 10.1177/1535370215570817
ER  - 

@article{
author = "Arsenović-Ranin, Nevena and Kosec, Duško and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Stojić-Vukanić, Zorica and Đikić, Jasmina and Bufan, Biljana and Leposavić, Gordana",
year = "2015",
abstract = "The study examined the putative role of ovarian hormones in shaping of rat peripheral T-cell compartment during post-reproductive period. In 20-month-old rats ovariectomized (Ox) at the very end of reproductive period, thymic output, cellularity and composition of major TCR alpha beta+peripheral blood lymphocyte and splenocyte subsets were analyzed. Ovariectomy led to the enlargement of CD8 + peripheral blood lymphocyte and splenocyte subpopulations. This reflected: (i) a more efficient thymic generation of CD8 + cells as indicated by increased number of CD4+CD8+double positive and the most mature CD4CD8+TCR alpha beta(high) thymocytes and CD8 + recent thymic emigrants (RTEs) in peripheral blood, but not in the spleen of Ox rats, and (ii) the expansion of CD8 + memory/activated peripheral blood lymphocytes and splenocytes. The latter was consistent with a greater frequency of proliferating cells among freshly isolated memory/activated CD8 + peripheral blood lymphocytes and splenocytes and increased proliferative response of CD8 + splenocytes to stimulation with plate-bound anti-CD3 antibody. The former could be related to the rise in splenic IL-7 and IL-15 mRNA expression. Although ovariectomy affected the overall number of CD4 + T cells in none of the examined compartments, it increased CD4+FoxP3 + peripheral blood lymphocyte and splenocyte counts by enhancing their generation in periphery. Collectively, the results suggest that ovariectomy-induced long-lasting disturbances in ovarian hormone levels (mirrored in diminished progesterone serum level in 20-month-old rats) affects both thymic CD8 + cell generation and peripheral homeostasis and leads to the expansion of CD4+FoxP3 + cells in the periphery, thereby enhancing autoreactive cell control on account of immune system efficacy to combat infections and tumors.",
publisher = "Sage Publications Ltd, London",
journal = "Experimental Biology and Medicine",
title = "Ovarian hormone level alterations during rat post-reproductive life-span influence CD8+T-cell homeostasis",
pages = "1332-1319",
number = "10",
volume = "240",
doi = "10.1177/1535370215570817"
}

Arsenović-Ranin, N., Kosec, D., Nacka-Aleksić, M., Pilipović, I., Stojić-Vukanić, Z., Đikić, J., Bufan, B.,& Leposavić, G.. (2015). Ovarian hormone level alterations during rat post-reproductive life-span influence CD8+T-cell homeostasis. in Experimental Biology and Medicine
Sage Publications Ltd, London., 240(10), 1319-1332.
https://doi.org/10.1177/1535370215570817

Arsenović-Ranin N, Kosec D, Nacka-Aleksić M, Pilipović I, Stojić-Vukanić Z, Đikić J, Bufan B, Leposavić G. Ovarian hormone level alterations during rat post-reproductive life-span influence CD8+T-cell homeostasis. in Experimental Biology and Medicine. 2015;240(10):1319-1332.
doi:10.1177/1535370215570817 .

Arsenović-Ranin, Nevena, Kosec, Duško, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Stojić-Vukanić, Zorica, Đikić, Jasmina, Bufan, Biljana, Leposavić, Gordana, "Ovarian hormone level alterations during rat post-reproductive life-span influence CD8+T-cell homeostasis" in Experimental Biology and Medicine, 240, no. 10 (2015):1319-1332,
https://doi.org/10.1177/1535370215570817 . .

TY  - JOUR
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Kosec, Duško
AU  - Bufan, Biljana
AU  - Arsenović-Ranin, Nevena
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2015
UR  - http://intor.torlakinstitut.com/handle/123456789/427
AB  - Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. (C) 2015 Elsevier Inc. All rights reserved.
PB  - Academic Press Inc Elsevier Science, San Diego
T2  - Brain Behavior and Immunity
T1  - Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level
EP  - 118
SP  - 101
VL  - 49
DO  - 10.1016/j.bbi.2015.04.017
ER  - 

@article{
author = "Nacka-Aleksić, Mirjana and Đikić, Jasmina and Pilipović, Ivan and Stojić-Vukanić, Zorica and Kosec, Duško and Bufan, Biljana and Arsenović-Ranin, Nevena and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2015",
abstract = "Compared with females, male Dark Agouti (DA) rats immunized for experimental autoimmune encephalomyelitis (EAE) with rat spinal cord homogenate in complete Freund's adjuvant (CFA) exhibited lower incidence of the disease, but the maximal neurological deficit was greater in the animals that developed the disease. Consistently, at the peak of the disease greater number of reactivated CD4+CD134+CD45RC- T lymphocytes was retrieved from male rat spinal cord. Their microglia/-macrophages were more activated and produced greater amount of prototypic proinflammatory cytokines in vitro. Additionally, oppositely to the expression of mRNAs for IL-12/p35, IL-10 and IL-27/p28, the expression of mRNA for IL-23/p19 was upregulated in male rat spinal cord mononuclear cells. Consequently, the IL-17+:IFN-gamma+ cell ratio within T lymphocytes from their spinal cord was skewed towards IL-17+ cells. Within this subpopulation, the IL-17+IFN-gamma+:IL-1 7+IL-10+ cell ratio was shifted towards IL-17+IFN-gamma+ cells, which have prominent tissue damaging capacity. This was associated with an upregulated expression of mRNAs for IL-1 beta and IL-6, but downregulated TGF-beta mRNA expression in male rat spinal cord mononuclear cells. The enhanced GM-CSF mRNA expression in these cells supported the greater pathogenicity of IL-17+ T lymphocytes infiltrating male spinal cord. In the inductive phase of the disease, contrary to the draining lymph node, in the spinal cord the frequency of CD 134+ cells among CD4+ T lymphocytes and the frequency of IL-17+ cells among T lymphocytes were greater in male than in female rats. This most likely reflected an enhanced transmigration of mononuclear cells into the spinal cord (judging by the lesser spinal cord CXCL12 mRNA expression), the greater frequency of activated microglia/macrophages and the increased expression of mRNAs for Th17 polarizing cytokines in male rat spinal cord mononuclear cells. Collectively, the results showed cellular and molecular mechanisms underlying the target organ specific sexual dimorphism in the T lymphocyte-dependent immune/inflammatory response, and suggested a substantial role for the target organ in shaping the sexually dimorphic clinical outcome of EAE. (C) 2015 Elsevier Inc. All rights reserved.",
publisher = "Academic Press Inc Elsevier Science, San Diego",
journal = "Brain Behavior and Immunity",
title = "Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level",
pages = "118-101",
volume = "49",
doi = "10.1016/j.bbi.2015.04.017"
}

Nacka-Aleksić, M., Đikić, J., Pilipović, I., Stojić-Vukanić, Z., Kosec, D., Bufan, B., Arsenović-Ranin, N., Dimitrijević, M.,& Leposavić, G.. (2015). Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level. in Brain Behavior and Immunity
Academic Press Inc Elsevier Science, San Diego., 49, 101-118.
https://doi.org/10.1016/j.bbi.2015.04.017

Nacka-Aleksić M, Đikić J, Pilipović I, Stojić-Vukanić Z, Kosec D, Bufan B, Arsenović-Ranin N, Dimitrijević M, Leposavić G. Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level. in Brain Behavior and Immunity. 2015;49:101-118.
doi:10.1016/j.bbi.2015.04.017 .

Nacka-Aleksić, Mirjana, Đikić, Jasmina, Pilipović, Ivan, Stojić-Vukanić, Zorica, Kosec, Duško, Bufan, Biljana, Arsenović-Ranin, Nevena, Dimitrijević, Mirjana, Leposavić, Gordana, "Male rats develop more severe experimental autoimmune encephalomyelitis than female rats: Sexual dimorphism and diergism at the spinal cord level" in Brain Behavior and Immunity, 49 (2015):101-118,
https://doi.org/10.1016/j.bbi.2015.04.017 . .

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  - Leposavić, Gordana
AU  - Perišić-Nanut, Milica
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Arsenović-Ranin, Nevena
AU  - Stojić-Vukanić, Zorica
AU  - Đikić, Jasmina
AU  - Nacka-Aleksić, Mirjana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/421
AB  - This study explores the role of ovarian hormones in the phenotypic shaping of peripheral T-cell pool over the reproductive lifespan of rats. For this purpose, 2-month-old prepubertally ovariectomised (Ox) rats, showing oestrogen and progesterone deficiency, and 11-month-old Ox rats, exhibiting only progesterone deficiency, were examined for thymus output, and cellularity and composition of major TCR alpha beta+ peripheral blood lymphocyte (PBL) and splenocyte subsets. Although ovariectomy increased thymic output in both 2- and 11-month-old rats, the count of both CD4+ and CD8+ PBLs and splenocytes increased only in the former. In the blood and spleen of 11-month-old Ox rats only the count of CD8+ cells increased. Although ovariectomy affected the total CD4+ count in none of the examined compartments from the 11-month-old rats, it increased CD4+FoxP3+ PBL and splenocyte relative proportions over those in the age-matched controls. The age-related differences in the cellularity and the major subset composition in Ox rats were linked to the differences in the ovarian steroid hormone levels registered in 2- and 11-month-old rats. The administration of progesterone to Ox rats during the seven days before the sacrificing confirmed contribution of this hormone deficiency to the ovariectomy-induced changes in the TCR alpha beta+ PBL and splenocyte pool from 11-month-old rats. The expansion of the CD8+ splenocyte subset in the 11-month-old Ox rats reflected increases in cellularity of memory and, particularly, nave cells. This was due to greater thymic output of CD8+ cells and homeostatic proliferation than apoptosis in 11-month-old Ox rats when compared with age-matched sham-Ox control rats. The homeostatic changes within CD8+ splenocyte pool from 11-month-old Ox rats, most likely, reflected the enhanced splenic IL-7 and TGF-beta mRNA expression. Overall, in adult female rats, circulating oestrogen and progesterone provide maintenance of T-cell counts, a diversity of T-cell repertoire, and the main T-cell subset composition in the periphery. Progesterone deficiency affects mainly the CD8+ lymphocyte compartment through increasing thymic CD8+ cell export and upsetting homeostatic regulation within the CD8+ splenocyte pool. These alterations were reversible through progesterone supplementation. (C) 2013 Elsevier GmbH, All rights reserved.
PB  - Elsevier Gmbh, Munich
T2  - Immunobiology
T1  - Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency
EP  - 130
IS  - 2
SP  - 118
VL  - 219
DO  - 10.1016/j.imbio.2013.08.004
ER  - 

@article{
author = "Leposavić, Gordana and Perišić-Nanut, Milica and Pilipović, Ivan and Kosec, Duško and Arsenović-Ranin, Nevena and Stojić-Vukanić, Zorica and Đikić, Jasmina and Nacka-Aleksić, Mirjana",
year = "2014",
abstract = "This study explores the role of ovarian hormones in the phenotypic shaping of peripheral T-cell pool over the reproductive lifespan of rats. For this purpose, 2-month-old prepubertally ovariectomised (Ox) rats, showing oestrogen and progesterone deficiency, and 11-month-old Ox rats, exhibiting only progesterone deficiency, were examined for thymus output, and cellularity and composition of major TCR alpha beta+ peripheral blood lymphocyte (PBL) and splenocyte subsets. Although ovariectomy increased thymic output in both 2- and 11-month-old rats, the count of both CD4+ and CD8+ PBLs and splenocytes increased only in the former. In the blood and spleen of 11-month-old Ox rats only the count of CD8+ cells increased. Although ovariectomy affected the total CD4+ count in none of the examined compartments from the 11-month-old rats, it increased CD4+FoxP3+ PBL and splenocyte relative proportions over those in the age-matched controls. The age-related differences in the cellularity and the major subset composition in Ox rats were linked to the differences in the ovarian steroid hormone levels registered in 2- and 11-month-old rats. The administration of progesterone to Ox rats during the seven days before the sacrificing confirmed contribution of this hormone deficiency to the ovariectomy-induced changes in the TCR alpha beta+ PBL and splenocyte pool from 11-month-old rats. The expansion of the CD8+ splenocyte subset in the 11-month-old Ox rats reflected increases in cellularity of memory and, particularly, nave cells. This was due to greater thymic output of CD8+ cells and homeostatic proliferation than apoptosis in 11-month-old Ox rats when compared with age-matched sham-Ox control rats. The homeostatic changes within CD8+ splenocyte pool from 11-month-old Ox rats, most likely, reflected the enhanced splenic IL-7 and TGF-beta mRNA expression. Overall, in adult female rats, circulating oestrogen and progesterone provide maintenance of T-cell counts, a diversity of T-cell repertoire, and the main T-cell subset composition in the periphery. Progesterone deficiency affects mainly the CD8+ lymphocyte compartment through increasing thymic CD8+ cell export and upsetting homeostatic regulation within the CD8+ splenocyte pool. These alterations were reversible through progesterone supplementation. (C) 2013 Elsevier GmbH, All rights reserved.",
publisher = "Elsevier Gmbh, Munich",
journal = "Immunobiology",
title = "Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency",
pages = "130-118",
number = "2",
volume = "219",
doi = "10.1016/j.imbio.2013.08.004"
}

Leposavić, G., Perišić-Nanut, M., Pilipović, I., Kosec, D., Arsenović-Ranin, N., Stojić-Vukanić, Z., Đikić, J.,& Nacka-Aleksić, M.. (2014). Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency. in Immunobiology
Elsevier Gmbh, Munich., 219(2), 118-130.
https://doi.org/10.1016/j.imbio.2013.08.004

Leposavić G, Perišić-Nanut M, Pilipović I, Kosec D, Arsenović-Ranin N, Stojić-Vukanić Z, Đikić J, Nacka-Aleksić M. Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency. in Immunobiology. 2014;219(2):118-130.
doi:10.1016/j.imbio.2013.08.004 .

Leposavić, Gordana, Perišić-Nanut, Milica, Pilipović, Ivan, Kosec, Duško, Arsenović-Ranin, Nevena, Stojić-Vukanić, Zorica, Đikić, Jasmina, Nacka-Aleksić, Mirjana, "Reshaping of T-lymphocyte compartment in adult prepubertaly ovariectomised rats: A putative role for progesterone deficiency" in Immunobiology, 219, no. 2 (2014):118-130,
https://doi.org/10.1016/j.imbio.2013.08.004 . .

TY  - JOUR
AU  - Đikić, Jasmina
AU  - Nacka-Aleksić, Mirjana
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Bufan, Biljana
AU  - Kosec, Duško
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/406
AB  - Aging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCR alpha beta+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naive CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory properties. Compared with young rats, following short-term PMA and ionomycin stimulation in vitro, the frequency of IL-17+ and IFN-gamma+CD4+ T lymphocytes among the spinal cord mononuclear cells from aged rats and the cytokine expression density on a per lymphocyte basis were reduced. Additionally, the increase in the proportion of autoregulatory IL-17+IL-10+ cells on the account of proinflammatory IL-17+IFN-gamma+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity in aged rats. This most likely reflected alterations in the aged rat spinal cord cytokine milieu, which were mirrored in a diminished expression of IL-1 beta mRNA followed by an enhanced expression of IL-6 and TGF-beta mRNA. Overall, the study points to age-related changes in T lymphocytes and other cells from the spinal cord infiltrate which could contribute to the decreased susceptibility of aged rats to the induction of EAE. (C) 2014 Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis
EP  - 197
SP  - 179
VL  - 58
DO  - 10.1016/j.exger.2014.08.005
ER  - 

@article{
author = "Đikić, Jasmina and Nacka-Aleksić, Mirjana and Pilipović, Ivan and Stojić-Vukanić, Zorica and Bufan, Biljana and Kosec, Duško and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2014",
abstract = "Aging is associated with the decline in immune response to infectious agents and tumors and increasing risk of autoimmunity, but the incidence of autoimmune diseases does not increase in the elderly. To elucidate the cellular and molecular mechanisms influencing clinical expression of autoimmunity in aged animals, the phenotypic and functional characteristics of mononuclear cells isolated from the spinal cords of 3-month-old (young) and 26-month-old (aged) Dark Agouti rats immunized to induce experimental autoimmune encephalomyelitis (EAE) - the model of multiple sclerosis, the most common autoimmune disease of the central nervous system, were examined. Aged rats were less susceptible to EAE induction, and the neurological and histological picture was milder in those rats which developed the clinically manifested disease. At the peak of the disease, several times fewer mononuclear cells and T lymphocytes were isolated from the spinal cords of aged rats compared with the young ones. The frequency of CD4+ cells among TCR alpha beta+ lymphocytes, as well as that of reactivated CD134(OX40)+ cells within its CD4+ T-lymphocyte subpopulation, was less in spinal cords of aged compared with young rats. Additionally, CD134 surface density on CD4+ lymphocytes was decreased in the spinal cord of aged rats. The changes in CD134 expression most likely reflected in part age-related intrinsic changes in CD4+ lymphocytes as the expression of this molecule was also impaired on in vitro stimulated naive CD4+ splenocytes from aged rats compared with young animals. In addition, greater frequency of CD8+ lymphocytes with regulatory phenotypes could also contribute to impaired CD4+ cell reactivation in aged rats. The increased apoptosis of CD4+ cells from aged rats was consistent with their impaired reactivation and it was accompanied by the greater frequency of CD4+CD11b+CD45(int/high) cells, which are supposed to be actively engaged in apoptotic cell phagocytosis and to have immunoregulatory properties. Compared with young rats, following short-term PMA and ionomycin stimulation in vitro, the frequency of IL-17+ and IFN-gamma+CD4+ T lymphocytes among the spinal cord mononuclear cells from aged rats and the cytokine expression density on a per lymphocyte basis were reduced. Additionally, the increase in the proportion of autoregulatory IL-17+IL-10+ cells on the account of proinflammatory IL-17+IFN-gamma+ cells within IL-17+ lymphocytes suggested their lower pathogenic capacity in aged rats. This most likely reflected alterations in the aged rat spinal cord cytokine milieu, which were mirrored in a diminished expression of IL-1 beta mRNA followed by an enhanced expression of IL-6 and TGF-beta mRNA. Overall, the study points to age-related changes in T lymphocytes and other cells from the spinal cord infiltrate which could contribute to the decreased susceptibility of aged rats to the induction of EAE. (C) 2014 Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis",
pages = "197-179",
volume = "58",
doi = "10.1016/j.exger.2014.08.005"
}

Đikić, J., Nacka-Aleksić, M., Pilipović, I., Stojić-Vukanić, Z., Bufan, B., Kosec, D., Dimitrijević, M.,& Leposavić, G.. (2014). Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 58, 179-197.
https://doi.org/10.1016/j.exger.2014.08.005

Đikić J, Nacka-Aleksić M, Pilipović I, Stojić-Vukanić Z, Bufan B, Kosec D, Dimitrijević M, Leposavić G. Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis. in Experimental Gerontology. 2014;58:179-197.
doi:10.1016/j.exger.2014.08.005 .

Đikić, Jasmina, Nacka-Aleksić, Mirjana, Pilipović, Ivan, Stojić-Vukanić, Zorica, Bufan, Biljana, Kosec, Duško, Dimitrijević, Mirjana, Leposavić, Gordana, "Age-associated changes in rat immune system: Lessons learned from experimental autoimmune encephalomyelitis" in Experimental Gerontology, 58 (2014):179-197,
https://doi.org/10.1016/j.exger.2014.08.005 . .

TY  - JOUR
AU  - Bufan, Biljana
AU  - Đikić, Jasmina
AU  - Nacka-Aleksić, Mirjana
AU  - Stojić-Vukanić, Zorica
AU  - Dimitrijević, Mirjana
AU  - Leposavić, Gordana
PY  - 2014
UR  - http://intor.torlakinstitut.com/handle/123456789/401
AB  - Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.
PB  - Društvo genetičara Srbije, Beograd
T2  - Genetika-Belgrade
T1  - Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression
EP  - 301
IS  - 1
SP  - 287
VL  - 46
DO  - 10.2298/GENSR1401287B
ER  - 

@article{
author = "Bufan, Biljana and Đikić, Jasmina and Nacka-Aleksić, Mirjana and Stojić-Vukanić, Zorica and Dimitrijević, Mirjana and Leposavić, Gordana",
year = "2014",
abstract = "Experimental autoimmune encephalomyelitis (EAE) is an animal model of multiple sclerosis, a prototype of Th1/Th17-mediated organ-specific autoimmune disease. In the rat, susceptibility to development of these diseases is shown to be strain-and age-dependent. In adult rats of distinct strains, it correlates with splenic dendritic cell (DC) subset composition, which also exhibit age-related changes. The aim of this study was to examine influence of aging on: i) Albino Oxford (relatively resistant to EAE) and Dark Agouti (susceptible to EAE) rat development of EAE and ii) their splenic conventional (OX62+) DC population in respect to its subset composition and expression of mRNAs for proinflammatory and immunosuppressive cytokines. We used 3-month-old (young) and 26-month-old (aged) rats of AO and DA strain. The rats were immunized for EAE with rat spinal cord homogenate in complete Freund's adjuvant and clinical course of the disease was followed. Fresh OX62+DCs were examined for the expression of CD4 (using flow cytometry) and genes encoding cytokines influencing DC activation/maturation (TNF-alpha and IL-6) using RT-PCR. Additionally, in vitro lipopolysaccharide (LPS) activated/matured DCs were examined for the expression of genes encoding cytokines controlling Th1/Th17 cell polarization using RT-PCR. With aging, AO rats became more susceptible, whereas DA rats largely lose their susceptibility to the induction of EAE. In AO rats aging shifted CD4+: CD4-DC ratio towards CD4- cells, producing large amount of proinflammatory cytokines, whereas in DA rats CD4+: CD4-DC ratio remained stable with aging. In fresh DCs from rats of both the strains the expression of TNF-alpha mRNA increased with aging, whereas that of IL-6 mRNA decreased and increased in DCs from AO and DA rats, respectively. Following in vitro LPS stimulation OX62+ DCs from aged AO rats up-regulated the expression of mRNA for IL-23p19 (specific subunit of IL-23; crucial for sustained IL-17 production) and IL-1 beta (positive IL-17 regulator), whereas down-regulated the expression of IL-10 (negative IL-17 regulator) when compared with young strain-matched rats. In DA rats aging incresed IL-23p19 mRNA expression in LPS-stimulated DCs, whereas exerted the opposing effects on the expression of mRNAs for IL-10 and IL-1 beta compared to AO rats. Irrespective of the rat strain, aging did not influence mRNA expression for IL-12p35 (driving Th1 polarization) in DCs. Overall, results suggest role of changes in the expression of genes encoding proinflammatory and immunosuppressive cytokines in development of age-related alterations in rat susceptibility to EAE induction.",
publisher = "Društvo genetičara Srbije, Beograd",
journal = "Genetika-Belgrade",
title = "Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression",
pages = "301-287",
number = "1",
volume = "46",
doi = "10.2298/GENSR1401287B"
}

Bufan, B., Đikić, J., Nacka-Aleksić, M., Stojić-Vukanić, Z., Dimitrijević, M.,& Leposavić, G.. (2014). Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression. in Genetika-Belgrade
Društvo genetičara Srbije, Beograd., 46(1), 287-301.
https://doi.org/10.2298/GENSR1401287B

Bufan B, Đikić J, Nacka-Aleksić M, Stojić-Vukanić Z, Dimitrijević M, Leposavić G. Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression. in Genetika-Belgrade. 2014;46(1):287-301.
doi:10.2298/GENSR1401287B .

Bufan, Biljana, Đikić, Jasmina, Nacka-Aleksić, Mirjana, Stojić-Vukanić, Zorica, Dimitrijević, Mirjana, Leposavić, Gordana, "Strain-specific differences in age-related changes in rat susceptibility to experimental autoimmune encephalomyelitis and dendritic cell cytokine gene expression" in Genetika-Belgrade, 46, no. 1 (2014):287-301,
https://doi.org/10.2298/GENSR1401287B . .

TY  - CONF
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Arsenović-Ranin, Nevena
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Đikić, Jasmina
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/849
AB  - Almost all cellular components of innate and adaptive immunity undergo age-related remodeling. The findings on age-related
changes in human and mouse dendritic cells (DCs) are conflicting, whereas there is no data on the influence of aging on rat DCs. In
attempt to fill this gap, freshly isolated splenic conventional OX62+ DCs from 3- (young) and 26-month-old (aged) Albino Oxford rats
were examined for subset composition, cell surface expression of activation markers (CD80, CD86 and CD40 and MHC II molecules)
and endocytic capacity using flow cytometric analysis (FCA). In addition, splenic OX62+ DCs isolated from rats of both ages were
cultured in the presence or in the absence of LPS. These cells were examined for the activation marker and TNF-α, IL-6, IL-12, IL-23,
TGF-β1, IL-10 expression using FCA, and RT-PCR and ELISA, respectively. Moreover, the allostimulatory capacity of OX62+ DCs and
allogeneic CD4+ T cell cytokine (IFN-γ, IL-4 and IL-17) production in MLR was quantified using FCA and ELISA, respectively. It was
found that aging: i) in OX62+ DCs population leads to a shift in CD4+:CD4- cell ratio towards CD4- cells and ii) influences OX62+
DCs maturation capacity (judging by activation marker expression and efficiency of endocytosis) by affecting action of intrinsic (TNF-
α and IL-10) and extrinsic regulatory factor expression. Furthermore, in LPS-matured OX62+ DCs from aged rats TNF-α, IL-12, IL-23
and IL-6 expression was increased, while IL-10 expression was diminished. Moreover, in MLR, OX62+ DCs from aged rats exhibited
enhanced Th1/Th17 driving force and diminished allostimulatory capacity.
PB  - Frontiers Media
C3  - Frontiers in Immunology, 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug
T1  - Age-associated shift in rat dendritic cell T-helper polarizing capacity
DO  - 10.3389/conf.fimmu.2013.02.00138
ER  - 

@conference{
author = "Bufan, Biljana and Stojić-Vukanić, Zorica and Arsenović-Ranin, Nevena and Kosec, Duško and Pilipović, Ivan and Perišić, Milica and Đikić, Jasmina and Leposavić, Gordana",
year = "2013",
abstract = "Almost all cellular components of innate and adaptive immunity undergo age-related remodeling. The findings on age-related
changes in human and mouse dendritic cells (DCs) are conflicting, whereas there is no data on the influence of aging on rat DCs. In
attempt to fill this gap, freshly isolated splenic conventional OX62+ DCs from 3- (young) and 26-month-old (aged) Albino Oxford rats
were examined for subset composition, cell surface expression of activation markers (CD80, CD86 and CD40 and MHC II molecules)
and endocytic capacity using flow cytometric analysis (FCA). In addition, splenic OX62+ DCs isolated from rats of both ages were
cultured in the presence or in the absence of LPS. These cells were examined for the activation marker and TNF-α, IL-6, IL-12, IL-23,
TGF-β1, IL-10 expression using FCA, and RT-PCR and ELISA, respectively. Moreover, the allostimulatory capacity of OX62+ DCs and
allogeneic CD4+ T cell cytokine (IFN-γ, IL-4 and IL-17) production in MLR was quantified using FCA and ELISA, respectively. It was
found that aging: i) in OX62+ DCs population leads to a shift in CD4+:CD4- cell ratio towards CD4- cells and ii) influences OX62+
DCs maturation capacity (judging by activation marker expression and efficiency of endocytosis) by affecting action of intrinsic (TNF-
α and IL-10) and extrinsic regulatory factor expression. Furthermore, in LPS-matured OX62+ DCs from aged rats TNF-α, IL-12, IL-23
and IL-6 expression was increased, while IL-10 expression was diminished. Moreover, in MLR, OX62+ DCs from aged rats exhibited
enhanced Th1/Th17 driving force and diminished allostimulatory capacity.",
publisher = "Frontiers Media",
journal = "Frontiers in Immunology, 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug",
title = "Age-associated shift in rat dendritic cell T-helper polarizing capacity",
doi = "10.3389/conf.fimmu.2013.02.00138"
}

Bufan, B., Stojić-Vukanić, Z., Arsenović-Ranin, N., Kosec, D., Pilipović, I., Perišić, M., Đikić, J.,& Leposavić, G.. (2013). Age-associated shift in rat dendritic cell T-helper polarizing capacity. in Frontiers in Immunology, 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug
Frontiers Media..
https://doi.org/10.3389/conf.fimmu.2013.02.00138

Bufan B, Stojić-Vukanić Z, Arsenović-Ranin N, Kosec D, Pilipović I, Perišić M, Đikić J, Leposavić G. Age-associated shift in rat dendritic cell T-helper polarizing capacity. in Frontiers in Immunology, 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug. 2013;.
doi:10.3389/conf.fimmu.2013.02.00138 .

Bufan, Biljana, Stojić-Vukanić, Zorica, Arsenović-Ranin, Nevena, Kosec, Duško, Pilipović, Ivan, Perišić, Milica, Đikić, Jasmina, Leposavić, Gordana, "Age-associated shift in rat dendritic cell T-helper polarizing capacity" in Frontiers in Immunology, 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug (2013),
https://doi.org/10.3389/conf.fimmu.2013.02.00138 . .

TY  - JOUR
AU  - Perišić, Milica
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Arsenović-Ranin, Nevena
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/396
AB  - The study explored the putative role of ovarian hormones in the peripubertal remodelling of peripheral T-cell compartment. Ovariectomy at age of 1 month enhanced the peripubertal rise in CD4+ and CD8+ cell numbers in peripheral blood (PB) and spleen from 2-month-old rats. This reflected maintenance of thymopoietic efficiency at the prepubertal level (judging by numbers of the most mature CD4+ and CD8+ thymocytes and recent thymic emigrants) and alterations in T-cell survival/proliferation in the periphery. Compared with age-matched controls, the frequency of apoptotic cells among CD8+ peripheral blood lymphocytes (PBLs) and CD4+ and CD8+ splenocytes was diminished in ovariectomized (Ox) rats, at least partly, due to lower CD95 surface density. The diminished frequency of the apoptotic T splenocytes could also be associated with the rise in the amount of splenic IL-7 mRNA. Additionally, the latter finding was consistent with the augmented proliferation of CD4+ and CD8+ splenocytes. However, the enhanced proliferation of these cells could also be linked to the rise in IL-2 receptor surface density. This increase was related to the enhanced splenic TNF-alpha mRNA expression. Additionally, ovariectomy led to the phenotypic alterations in the major PBL and splenic T-cell subsets by diminishing/preventing the peripubertal changes in the frequency of cells at distinct stages of post-thymic differentiation/maturation (recent thymic emigrants, mature naive and memory cells), and by decreasing the frequency of NKT cells within peripheral CD8+ subsets. In addition to numerical and phenotypic changes in T-cell compartment (due to the lack of ovarian hormone action at both the thymic and peripheral level), Ox rats exhibited a much larger delayed-type hypersensitivity (DTH) response compared with age-matched controls. This suggested the augmented T-cell-mediated immune response in Ox rats compared with aged-matched controls. (C) 2012 Elsevier GmbH. All rights reserved.
PB  - Elsevier Gmbh, Urban & Fischer Verlag, Jena
T2  - Immunobiology
T1  - Role of ovarian hormones in T-cell homeostasis: From the thymus to the periphery
EP  - 367
IS  - 3
SP  - 353
VL  - 218
DO  - 10.1016/j.imbio.2012.05.009
ER  - 

@article{
author = "Perišić, Milica and Stojić-Vukanić, Zorica and Pilipović, Ivan and Kosec, Duško and Nacka-Aleksić, Mirjana and Đikić, Jasmina and Arsenović-Ranin, Nevena and Leposavić, Gordana",
year = "2013",
abstract = "The study explored the putative role of ovarian hormones in the peripubertal remodelling of peripheral T-cell compartment. Ovariectomy at age of 1 month enhanced the peripubertal rise in CD4+ and CD8+ cell numbers in peripheral blood (PB) and spleen from 2-month-old rats. This reflected maintenance of thymopoietic efficiency at the prepubertal level (judging by numbers of the most mature CD4+ and CD8+ thymocytes and recent thymic emigrants) and alterations in T-cell survival/proliferation in the periphery. Compared with age-matched controls, the frequency of apoptotic cells among CD8+ peripheral blood lymphocytes (PBLs) and CD4+ and CD8+ splenocytes was diminished in ovariectomized (Ox) rats, at least partly, due to lower CD95 surface density. The diminished frequency of the apoptotic T splenocytes could also be associated with the rise in the amount of splenic IL-7 mRNA. Additionally, the latter finding was consistent with the augmented proliferation of CD4+ and CD8+ splenocytes. However, the enhanced proliferation of these cells could also be linked to the rise in IL-2 receptor surface density. This increase was related to the enhanced splenic TNF-alpha mRNA expression. Additionally, ovariectomy led to the phenotypic alterations in the major PBL and splenic T-cell subsets by diminishing/preventing the peripubertal changes in the frequency of cells at distinct stages of post-thymic differentiation/maturation (recent thymic emigrants, mature naive and memory cells), and by decreasing the frequency of NKT cells within peripheral CD8+ subsets. In addition to numerical and phenotypic changes in T-cell compartment (due to the lack of ovarian hormone action at both the thymic and peripheral level), Ox rats exhibited a much larger delayed-type hypersensitivity (DTH) response compared with age-matched controls. This suggested the augmented T-cell-mediated immune response in Ox rats compared with aged-matched controls. (C) 2012 Elsevier GmbH. All rights reserved.",
publisher = "Elsevier Gmbh, Urban & Fischer Verlag, Jena",
journal = "Immunobiology",
title = "Role of ovarian hormones in T-cell homeostasis: From the thymus to the periphery",
pages = "367-353",
number = "3",
volume = "218",
doi = "10.1016/j.imbio.2012.05.009"
}

Perišić, M., Stojić-Vukanić, Z., Pilipović, I., Kosec, D., Nacka-Aleksić, M., Đikić, J., Arsenović-Ranin, N.,& Leposavić, G.. (2013). Role of ovarian hormones in T-cell homeostasis: From the thymus to the periphery. in Immunobiology
Elsevier Gmbh, Urban & Fischer Verlag, Jena., 218(3), 353-367.
https://doi.org/10.1016/j.imbio.2012.05.009

Perišić M, Stojić-Vukanić Z, Pilipović I, Kosec D, Nacka-Aleksić M, Đikić J, Arsenović-Ranin N, Leposavić G. Role of ovarian hormones in T-cell homeostasis: From the thymus to the periphery. in Immunobiology. 2013;218(3):353-367.
doi:10.1016/j.imbio.2012.05.009 .

Perišić, Milica, Stojić-Vukanić, Zorica, Pilipović, Ivan, Kosec, Duško, Nacka-Aleksić, Mirjana, Đikić, Jasmina, Arsenović-Ranin, Nevena, Leposavić, Gordana, "Role of ovarian hormones in T-cell homeostasis: From the thymus to the periphery" in Immunobiology, 218, no. 3 (2013):353-367,
https://doi.org/10.1016/j.imbio.2012.05.009 . .

TY  - JOUR
AU  - Arsenović-Ranin, Nevena
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Perišić, Milica
AU  - Kosec, Duško
AU  - Pilipović, Ivan
AU  - Stojić-Vukanić, Zorica
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/372
AB  - The study was aimed to define the putative role of ovarian hormones in shaping thymocyte apoptosis and proliferation during thymic involution. Thymocytes from young adult and middle-aged rats ovariectomized (Ox) before puberty were examined for apoptosis and proliferation. Apoptosis and proliferation were measured in fresh thymocyte suspensions and in their 18-hour cultures, and fresh thymocyte suspensions, respectively. The thymocyte population and the major thymocyte subsets were analyzed following triple staining using anti-CD4 and anti-CD8 monoclonal antibodies and 7-AAD to label apoptotic or proliferating cells. The frequency of apoptotic cells was lower in thymocyte suspensions and cultures from Ox rats of both ages. This reflected in a diminished frequency of apoptotic cells amongst CD4+CD8+ double positive (DP) and CD4+CD8- single positive (SP), and DP cells in young and middle-aged Ox rats, respectively. Additionally, in thymocyte cultures from Ox rats the frequency of apoptotic cells amongst CD4+CD8- and CD4-CD8+ SP cells decreased with age, but increased within DP and CD4-CD8- double negative (DN) subsets, reaching in the former subset from middle-aged Ox rats higher values than in age-matched controls. The frequency of proliferating cells was also lower in Ox rats than in controls. This reflected the lower frequency of cycling cells amongst CD4+CD8- SP and CD4-CD8+ SP thymocytes in young rats, and DP and CD4-CD8+ SP thymocytes in middle-aged rats. Besides, in both SP and DP thymocyte subsets from Ox rats the frequency of proliferating cells declined with age. In conclusion, thymocyte apoptosis and proliferation exhibit ovarian hormone-dependent thymocyte subset specific alterations during thymic involution.
AB  - Cilj istraživanja je bio da se definiše značaj hormona ovarijuma za razvoj promena u apoptozi i proliferaciji timocita tokom involucije timusa. U tom cilju apoptoza i proliferacija timocita ispitivana je kod prepubertetno ovariektomisanih (Ox) mladih (uzrasta 2 meseca) i sredovečnih pacova (uzrasta 11 meseci). Apoptoza je određivana u suspenziji sveže izolovanih timocita i nakon njihove 18- časovne kultivacije, a proliferacija u suspenziji sveže izolovanih timocita. Procenat apoptotičnih i proliferišućih ćelija je određivan u celokupnoj populaciji timocita, i unutar glavnih subpopulacija ovih ćelija, koje su razdvojene na osnovu ekspresije CD4/CD8 molekula, metodom protočne fluorocitometrije, korišćenjem 7-aminoaktinomicina D (7-AAD). Procenat ćelija u apoptozi je bio značajno manji u suspenzijama svežih timocita koji su izolovani iz Ox životinja i u njihovim kulturama nego u onim izolovanim iz kontrolnih životinja. Ovaj nalaz je odražavao smanjenu učestalost ćelija u apoptozi u CD4+CD8+ dvostruko pozitivnoj (DP) i CD4+CD8- jednostruko pozitivnoj (JP) subpopulaciji timocita kod mladih i u DP subpopulaciji kod sredovečnih Ox pacova. U kulturama timocita koji su izolovani iz sredovečnih Ox pacova uočeno je smanjenje učestalosti ćelija u apoptozi unutar subpopulacija CD4+CD8- i CD4-CD8+ JP timocita, a povećanje unutar DP i CD4-CD8- dvostruko negativne (DN) subpopulacije ovih ćelija. Učestalost proliferišućih ćelija je takođe bila niža u suspenzijama timocita izolovanih iz Ox pacova nego u onim izolovanim iz kontrolnih životinja. Ovo je odražavalo smanjenu proliferaciju CD4+CD8- i CD4-CD8+ JP timocita kod mladih, a DP i CD4-CD8+ JP timocita kod sredovečnih pacova. Procentualna zastupljenost proliferišućih ćelija u subpopulacijama JP i DP timocita je bila veća kod mladih nego kod sredovečnih Ox pacova. U zaključku, tokom involucije timusa dolazi do promena u apoptozi i proliferaciji timocita koje su specifične za pojedine subpopulacije timocita i zavisne od prisustva hormona ovarijuma.
PB  - Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd
T2  - Acta veterinaria - Beograd
T1  - Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner
T1  - Hormoni ovarijuma imaju različit uticaj na modelovanje apoptoze i proliferacije unutar različitih subpopulacija timocita tokom involucije timusa
EP  - 21
IS  - 1
SP  - 3
VL  - 63
DO  - 10.2298/AVB1301003A
ER  - 

@article{
author = "Arsenović-Ranin, Nevena and Nacka-Aleksić, Mirjana and Đikić, Jasmina and Perišić, Milica and Kosec, Duško and Pilipović, Ivan and Stojić-Vukanić, Zorica and Leposavić, Gordana",
year = "2013",
abstract = "The study was aimed to define the putative role of ovarian hormones in shaping thymocyte apoptosis and proliferation during thymic involution. Thymocytes from young adult and middle-aged rats ovariectomized (Ox) before puberty were examined for apoptosis and proliferation. Apoptosis and proliferation were measured in fresh thymocyte suspensions and in their 18-hour cultures, and fresh thymocyte suspensions, respectively. The thymocyte population and the major thymocyte subsets were analyzed following triple staining using anti-CD4 and anti-CD8 monoclonal antibodies and 7-AAD to label apoptotic or proliferating cells. The frequency of apoptotic cells was lower in thymocyte suspensions and cultures from Ox rats of both ages. This reflected in a diminished frequency of apoptotic cells amongst CD4+CD8+ double positive (DP) and CD4+CD8- single positive (SP), and DP cells in young and middle-aged Ox rats, respectively. Additionally, in thymocyte cultures from Ox rats the frequency of apoptotic cells amongst CD4+CD8- and CD4-CD8+ SP cells decreased with age, but increased within DP and CD4-CD8- double negative (DN) subsets, reaching in the former subset from middle-aged Ox rats higher values than in age-matched controls. The frequency of proliferating cells was also lower in Ox rats than in controls. This reflected the lower frequency of cycling cells amongst CD4+CD8- SP and CD4-CD8+ SP thymocytes in young rats, and DP and CD4-CD8+ SP thymocytes in middle-aged rats. Besides, in both SP and DP thymocyte subsets from Ox rats the frequency of proliferating cells declined with age. In conclusion, thymocyte apoptosis and proliferation exhibit ovarian hormone-dependent thymocyte subset specific alterations during thymic involution., Cilj istraživanja je bio da se definiše značaj hormona ovarijuma za razvoj promena u apoptozi i proliferaciji timocita tokom involucije timusa. U tom cilju apoptoza i proliferacija timocita ispitivana je kod prepubertetno ovariektomisanih (Ox) mladih (uzrasta 2 meseca) i sredovečnih pacova (uzrasta 11 meseci). Apoptoza je određivana u suspenziji sveže izolovanih timocita i nakon njihove 18- časovne kultivacije, a proliferacija u suspenziji sveže izolovanih timocita. Procenat apoptotičnih i proliferišućih ćelija je određivan u celokupnoj populaciji timocita, i unutar glavnih subpopulacija ovih ćelija, koje su razdvojene na osnovu ekspresije CD4/CD8 molekula, metodom protočne fluorocitometrije, korišćenjem 7-aminoaktinomicina D (7-AAD). Procenat ćelija u apoptozi je bio značajno manji u suspenzijama svežih timocita koji su izolovani iz Ox životinja i u njihovim kulturama nego u onim izolovanim iz kontrolnih životinja. Ovaj nalaz je odražavao smanjenu učestalost ćelija u apoptozi u CD4+CD8+ dvostruko pozitivnoj (DP) i CD4+CD8- jednostruko pozitivnoj (JP) subpopulaciji timocita kod mladih i u DP subpopulaciji kod sredovečnih Ox pacova. U kulturama timocita koji su izolovani iz sredovečnih Ox pacova uočeno je smanjenje učestalosti ćelija u apoptozi unutar subpopulacija CD4+CD8- i CD4-CD8+ JP timocita, a povećanje unutar DP i CD4-CD8- dvostruko negativne (DN) subpopulacije ovih ćelija. Učestalost proliferišućih ćelija je takođe bila niža u suspenzijama timocita izolovanih iz Ox pacova nego u onim izolovanim iz kontrolnih životinja. Ovo je odražavalo smanjenu proliferaciju CD4+CD8- i CD4-CD8+ JP timocita kod mladih, a DP i CD4-CD8+ JP timocita kod sredovečnih pacova. Procentualna zastupljenost proliferišućih ćelija u subpopulacijama JP i DP timocita je bila veća kod mladih nego kod sredovečnih Ox pacova. U zaključku, tokom involucije timusa dolazi do promena u apoptozi i proliferaciji timocita koje su specifične za pojedine subpopulacije timocita i zavisne od prisustva hormona ovarijuma.",
publisher = "Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd",
journal = "Acta veterinaria - Beograd",
title = "Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner, Hormoni ovarijuma imaju različit uticaj na modelovanje apoptoze i proliferacije unutar različitih subpopulacija timocita tokom involucije timusa",
pages = "21-3",
number = "1",
volume = "63",
doi = "10.2298/AVB1301003A"
}

Arsenović-Ranin, N., Nacka-Aleksić, M., Đikić, J., Perišić, M., Kosec, D., Pilipović, I., Stojić-Vukanić, Z.,& Leposavić, G.. (2013). Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner. in Acta veterinaria - Beograd
Univerzitet u Beogradu - Fakultet veterinarske medicine, Beograd., 63(1), 3-21.
https://doi.org/10.2298/AVB1301003A

Arsenović-Ranin N, Nacka-Aleksić M, Đikić J, Perišić M, Kosec D, Pilipović I, Stojić-Vukanić Z, Leposavić G. Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner. in Acta veterinaria - Beograd. 2013;63(1):3-21.
doi:10.2298/AVB1301003A .

Arsenović-Ranin, Nevena, Nacka-Aleksić, Mirjana, Đikić, Jasmina, Perišić, Milica, Kosec, Duško, Pilipović, Ivan, Stojić-Vukanić, Zorica, Leposavić, Gordana, "Thymocyte apoptosis and proliferation modeling during rat thymic involution is influenced by ovarian hormones in a thymocyte subset-specific manner" in Acta veterinaria - Beograd, 63, no. 1 (2013):3-21,
https://doi.org/10.2298/AVB1301003A . .

TY  - CONF
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Arsenović-Ranin, Nevena
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Nacka-Aleksić, Mirjana
AU  - Đikić, Jasmina
AU  - Perišić, Milica
AU  - Leposavić, Gordana
PY  - 2012
UR  - http://intor.torlakinstitut.com/handle/123456789/848
AB  - Starenje dovodi do promena skoro svnh komponenti urođenog i stečenog imuniteta. Brojna istraživanja kod čoveka i miša su pokazala promene u fenotipu i funkciji dendritskih ćelija (DĆ) takom starenja i ukazala na značajne specijes specifične razlike. Budući da nema podataka, a uticaju starenja na DĆ pacova, ispitivane su kanvencionalne OH62+ DĆ (kDĆ) izolovane iz slezina mladih (3 meseca) i starih (26 meseci) AO pacova. Određivana je zastupljenost glavnih subpopulacija ovih ćelija, ekspresija MHC II i kostimulatornih molekula i sposobnost preuzimanja antigena u suspenzijama sveže izolovanih ćelija, kao i njihove fenotiiske i funkcijske karakteristike nakon in vitro stimulacije lipopalisaharidom (LPS). U suspenziji sveže izolovanih slezinskih kDĆ starih nađena je veća zastupljenost CD11b+CD4- ćelija, manja površinska gustina CD80 i CD86 molekula (što ukazuje na manji stepen zrelosti) i pokazano da su one efikasnije u endocitoznoj aktivnosti posredovanoj manoznim receptorom. Ovi nalazi se mogu povezati sa većom količinom iRNK za IL-10 u frakciji ćelija slezine niske gustine starih pacova. Izraženija „spontana" aktivacija/maturacija kDĆ starih životinja u kulturi sugergiše da starenjem uslovljene promene u sazrevanju kDĆ in vivo najverovatnije nastaju usled supresivnog delovanja IL-10, koga produkuju ćelije iz njihovog okruženja. Nakon in vitro stimulacije LPS-om, kDĆ starih živatinja su ispoljile zreliji fenotipski profil u odnosu na kDĆ mladih životinja i pokazale izmenjenu sposobnost stimulacije alogenih  CD4+ T ćelija u mešanoj leukocitnoj reakciji. Osim taga, nakon stimulacije LPS-om, u kDĆ starih životinja je nađena povećana ekspresija iRNK za TNF-alfa (što bi, makar
delimično, moglo da o6jasni opisane fenotipske promene) i iRENK za IL-12/IL-23, p 40 i IL-23 p19, dok je ekspresija iRNK za IL-10 i IL-12 p35 bila smanjena. U zaključku, rezultati pokazuju da tokom ctapenja dolazi do promene u odnosu subpopulacija kDĆ u slezini, da se menja njihova sposobnost sazrevanja, alostimulatorni kapacitet i citokinski profil.
PB  - Društvo imunologa Srbije
C3  - Dani imunologije 2012, Imunski mehanizmi u očuvanju zdravlja i u bolesti
T1  - Uticaj starenja na fenotipske i funkcijske karakteristike dendritskih ćelija slezine pacova
UR  - https://hdl.handle.net/21.15107/rcub_intor_848
ER  - 

@conference{
author = "Bufan, Biljana and Stojić-Vukanić, Zorica and Arsenović-Ranin, Nevena and Pilipović, Ivan and Kosec, Duško and Nacka-Aleksić, Mirjana and Đikić, Jasmina and Perišić, Milica and Leposavić, Gordana",
year = "2012",
abstract = "Starenje dovodi do promena skoro svnh komponenti urođenog i stečenog imuniteta. Brojna istraživanja kod čoveka i miša su pokazala promene u fenotipu i funkciji dendritskih ćelija (DĆ) takom starenja i ukazala na značajne specijes specifične razlike. Budući da nema podataka, a uticaju starenja na DĆ pacova, ispitivane su kanvencionalne OH62+ DĆ (kDĆ) izolovane iz slezina mladih (3 meseca) i starih (26 meseci) AO pacova. Određivana je zastupljenost glavnih subpopulacija ovih ćelija, ekspresija MHC II i kostimulatornih molekula i sposobnost preuzimanja antigena u suspenzijama sveže izolovanih ćelija, kao i njihove fenotiiske i funkcijske karakteristike nakon in vitro stimulacije lipopalisaharidom (LPS). U suspenziji sveže izolovanih slezinskih kDĆ starih nađena je veća zastupljenost CD11b+CD4- ćelija, manja površinska gustina CD80 i CD86 molekula (što ukazuje na manji stepen zrelosti) i pokazano da su one efikasnije u endocitoznoj aktivnosti posredovanoj manoznim receptorom. Ovi nalazi se mogu povezati sa većom količinom iRNK za IL-10 u frakciji ćelija slezine niske gustine starih pacova. Izraženija „spontana" aktivacija/maturacija kDĆ starih životinja u kulturi sugergiše da starenjem uslovljene promene u sazrevanju kDĆ in vivo najverovatnije nastaju usled supresivnog delovanja IL-10, koga produkuju ćelije iz njihovog okruženja. Nakon in vitro stimulacije LPS-om, kDĆ starih živatinja su ispoljile zreliji fenotipski profil u odnosu na kDĆ mladih životinja i pokazale izmenjenu sposobnost stimulacije alogenih  CD4+ T ćelija u mešanoj leukocitnoj reakciji. Osim taga, nakon stimulacije LPS-om, u kDĆ starih životinja je nađena povećana ekspresija iRNK za TNF-alfa (što bi, makar
delimično, moglo da o6jasni opisane fenotipske promene) i iRENK za IL-12/IL-23, p 40 i IL-23 p19, dok je ekspresija iRNK za IL-10 i IL-12 p35 bila smanjena. U zaključku, rezultati pokazuju da tokom ctapenja dolazi do promene u odnosu subpopulacija kDĆ u slezini, da se menja njihova sposobnost sazrevanja, alostimulatorni kapacitet i citokinski profil.",
publisher = "Društvo imunologa Srbije",
journal = "Dani imunologije 2012, Imunski mehanizmi u očuvanju zdravlja i u bolesti",
title = "Uticaj starenja na fenotipske i funkcijske karakteristike dendritskih ćelija slezine pacova",
url = "https://hdl.handle.net/21.15107/rcub_intor_848"
}

Bufan, B., Stojić-Vukanić, Z., Arsenović-Ranin, N., Pilipović, I., Kosec, D., Nacka-Aleksić, M., Đikić, J., Perišić, M.,& Leposavić, G.. (2012). Uticaj starenja na fenotipske i funkcijske karakteristike dendritskih ćelija slezine pacova. in Dani imunologije 2012, Imunski mehanizmi u očuvanju zdravlja i u bolesti
Društvo imunologa Srbije..
https://hdl.handle.net/21.15107/rcub_intor_848

Bufan B, Stojić-Vukanić Z, Arsenović-Ranin N, Pilipović I, Kosec D, Nacka-Aleksić M, Đikić J, Perišić M, Leposavić G. Uticaj starenja na fenotipske i funkcijske karakteristike dendritskih ćelija slezine pacova. in Dani imunologije 2012, Imunski mehanizmi u očuvanju zdravlja i u bolesti. 2012;.
https://hdl.handle.net/21.15107/rcub_intor_848 .

Bufan, Biljana, Stojić-Vukanić, Zorica, Arsenović-Ranin, Nevena, Pilipović, Ivan, Kosec, Duško, Nacka-Aleksić, Mirjana, Đikić, Jasmina, Perišić, Milica, Leposavić, Gordana, "Uticaj starenja na fenotipske i funkcijske karakteristike dendritskih ćelija slezine pacova" in Dani imunologije 2012, Imunski mehanizmi u očuvanju zdravlja i u bolesti (2012),
https://hdl.handle.net/21.15107/rcub_intor_848 .

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  - 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 .