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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - CONF
AU  - Pešić, Vesna
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Leposavić, Gordana
PY  - 2006
UR  - http://intor.torlakinstitut.com/handle/123456789/219
PB  - Savez farmaceutskih udruženja Srbije, Beograd
C3  - Arhiv za farmaciju
T1  - Immunomodulation in ageing: Effects of β-adrenoceptor blockade on thymopoiesis
T1  - Imunomodulacija u starenju - uticaj blokade β-adrenergičkih receptora na timopoezu
EP  - 377
IS  - 4
SP  - 376
VL  - 56
UR  - https://hdl.handle.net/21.15107/rcub_intor_219
ER  - 

@conference{
author = "Pešić, Vesna and Kosec, Duško and Radojević, Katarina and Pilipović, Ivan and Perišić, Milica and Leposavić, Gordana",
year = "2006",
publisher = "Savez farmaceutskih udruženja Srbije, Beograd",
journal = "Arhiv za farmaciju",
title = "Immunomodulation in ageing: Effects of β-adrenoceptor blockade on thymopoiesis, Imunomodulacija u starenju - uticaj blokade β-adrenergičkih receptora na timopoezu",
pages = "377-376",
number = "4",
volume = "56",
url = "https://hdl.handle.net/21.15107/rcub_intor_219"
}

Pešić, V., Kosec, D., Radojević, K., Pilipović, I., Perišić, M.,& Leposavić, G.. (2006). Immunomodulation in ageing: Effects of β-adrenoceptor blockade on thymopoiesis. in Arhiv za farmaciju
Savez farmaceutskih udruženja Srbije, Beograd., 56(4), 376-377.
https://hdl.handle.net/21.15107/rcub_intor_219

Pešić V, Kosec D, Radojević K, Pilipović I, Perišić M, Leposavić G. Immunomodulation in ageing: Effects of β-adrenoceptor blockade on thymopoiesis. in Arhiv za farmaciju. 2006;56(4):376-377.
https://hdl.handle.net/21.15107/rcub_intor_219 .

Pešić, Vesna, Kosec, Duško, Radojević, Katarina, Pilipović, Ivan, Perišić, Milica, Leposavić, Gordana, "Immunomodulation in ageing: Effects of β-adrenoceptor blockade on thymopoiesis" in Arhiv za farmaciju, 56, no. 4 (2006):376-377,
https://hdl.handle.net/21.15107/rcub_intor_219 .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pešić, Vesna
AU  - Kosec, Duško
AU  - Radojević, Katarina
AU  - Arsenović-Ranin, Nevena
AU  - Pilipović, Ivan
AU  - Perišić, Milica
AU  - Plećaš-Solarović, Bosiljka
PY  - 2006
UR  - http://intor.torlakinstitut.com/handle/123456789/209
AB  - To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCR alpha beta and (ii) Thy-1, which is supposed to be a regulator of TCR alpha beta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCR alpha beta signalling in the development of CD4+25+T-reg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRao-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCR alpha beta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCR alpha beta(high) to the SP TCR alpha beta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T-reg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing. (c) 2006 Elsevier Inc. All rights reserved.
PB  - Pergamon-Elsevier Science Ltd, Oxford
T2  - Experimental Gerontology
T1  - Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats
EP  - 589
IS  - 6
SP  - 574
VL  - 41
DO  - 10.1016/j.exger.2006.03.006
ER  - 

@article{
author = "Leposavić, Gordana and Pešić, Vesna and Kosec, Duško and Radojević, Katarina and Arsenović-Ranin, Nevena and Pilipović, Ivan and Perišić, Milica and Plećaš-Solarović, Bosiljka",
year = "2006",
abstract = "To elucidate the effects of ageing on T-cell-maturation, in 3- and 18-month-old rats, we analysed the expression of: (i) CD4/CD8/TCR alpha beta and (ii) Thy-1, which is supposed to be a regulator of TCR alpha beta signalling, and thereby the thymocyte selection thresholds. Since an essential role for TCR alpha beta signalling in the development of CD4+25+T-reg-cells was suggested, the frequency of these cells was also quantified. We demonstrated that, as for mice, early thymocyte differentiational steps within the CD4-8- double negative (DN) developmental stage are age-sensitive. Furthermore, we revealed that TCRao-dependent stages of T-cell development are affected by ageing, most likely due to an impaired expression of Thy-1 on TCR alpha beta(low) thymocytes entering selection processes. The diminished frequency of the post-selection CD4+8+ double positive (DP) cells in aged rats, together with an overrepresentation of mature single positive (SP) cells, most probably suggests more efficient differentiational transition from the DP TCR alpha beta(high) to the SP TCR alpha beta(high) developmental stage, which is followed by an increase in pre-migration proliferation of the mature SP cells. Moreover, the study indicated impaired intrathymic generation of CD4+25+T-reg-cells in aged rats, thus providing a possible explanation for the increased frequency of autoimmune diseases in ageing. (c) 2006 Elsevier Inc. All rights reserved.",
publisher = "Pergamon-Elsevier Science Ltd, Oxford",
journal = "Experimental Gerontology",
title = "Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats",
pages = "589-574",
number = "6",
volume = "41",
doi = "10.1016/j.exger.2006.03.006"
}

Leposavić, G., Pešić, V., Kosec, D., Radojević, K., Arsenović-Ranin, N., Pilipović, I., Perišić, M.,& Plećaš-Solarović, B.. (2006). Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats. in Experimental Gerontology
Pergamon-Elsevier Science Ltd, Oxford., 41(6), 574-589.
https://doi.org/10.1016/j.exger.2006.03.006

Leposavić G, Pešić V, Kosec D, Radojević K, Arsenović-Ranin N, Pilipović I, Perišić M, Plećaš-Solarović B. Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats. in Experimental Gerontology. 2006;41(6):574-589.
doi:10.1016/j.exger.2006.03.006 .

Leposavić, Gordana, Pešić, Vesna, Kosec, Duško, Radojević, Katarina, Arsenović-Ranin, Nevena, Pilipović, Ivan, Perišić, Milica, Plećaš-Solarović, Bosiljka, "Age-associated changes in CD90 expression on thymocytes and in TCR-dependent stages of thymocyte maturation in male rats" in Experimental Gerontology, 41, no. 6 (2006):574-589,
https://doi.org/10.1016/j.exger.2006.03.006 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Arsenović-Ranin, Nevena
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Pešić, Vesna
AU  - Vidić-Danković, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Pilipović, Ivan
PY  - 2006
UR  - http://intor.torlakinstitut.com/handle/123456789/208
AB  - Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCR alpha beta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCR alpha beta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCR alpha beta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.
PB  - Springer, Dordrecht
T2  - Molecular and Cellular Biochemistry
T1  - Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis
EP  - 99
IS  - 1-2
SP  - 87
VL  - 285
DO  - 10.1007/s11010-005-9059-5
ER  - 

@article{
author = "Leposavić, Gordana and Arsenović-Ranin, Nevena and Radojević, Katarina and Kosec, Duško and Pešić, Vesna and Vidić-Danković, Biljana and Plećaš-Solarović, Bosiljka and Pilipović, Ivan",
year = "2006",
abstract = "Adult male Wistar rats were subjected to propranolol (P, 0.40 mg/100 g/day) or saline (S) administration (controls) over 14 days. The expression of major differentiation molecules on thymocytes and Thy-1 (CD90) molecules, which are shown to adjust thymocyte sensitivity to TCR alpha beta signaling, was studied. In addition, the sensitivity of thymocytes to induction of apoptosis and concanavalin A (Con A) signaling was estimated. The thymocytes from P-treated (PT) rats exhibited an increased sensitivity to induction of apoptosis, as well as to Con A stimulation. Furthermore, P treatment produced changes in the distribution of thymocyte subsets suggesting that more cells passed positive selection and further differentiated into mature CD4+ or CD8+ single positive (SP) TCR alpha beta(high) cells. These changes may, at least partly, be related to the markedly increased density of Thy-1 surface expression on TCR alpha beta(low) thymocytes from these rats. The increased frequency of cells expressing the CD4+25+ phenotype, which has been shown to be characteristic for regulatory cells in the thymus, may also indicate alterations in thymocyte selection following P treatment. Inasmuch as positive and negative selections play an important role in continuously reshaping the T-cell repertoire and maintaining tolerance, the hereby presented study suggests that pharmacological manipulations with beta-AR signaling, or chemically evoked alterations in catecholamine release, may interfere with the regulation of thymocyte selection, and consequently with the immune response.",
publisher = "Springer, Dordrecht",
journal = "Molecular and Cellular Biochemistry",
title = "Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis",
pages = "99-87",
number = "1-2",
volume = "285",
doi = "10.1007/s11010-005-9059-5"
}

Leposavić, G., Arsenović-Ranin, N., Radojević, K., Kosec, D., Pešić, V., Vidić-Danković, B., Plećaš-Solarović, B.,& Pilipović, I.. (2006). Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis. in Molecular and Cellular Biochemistry
Springer, Dordrecht., 285(1-2), 87-99.
https://doi.org/10.1007/s11010-005-9059-5

Leposavić G, Arsenović-Ranin N, Radojević K, Kosec D, Pešić V, Vidić-Danković B, Plećaš-Solarović B, Pilipović I. Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis. in Molecular and Cellular Biochemistry. 2006;285(1-2):87-99.
doi:10.1007/s11010-005-9059-5 .

Leposavić, Gordana, Arsenović-Ranin, Nevena, Radojević, Katarina, Kosec, Duško, Pešić, Vesna, Vidić-Danković, Biljana, Plećaš-Solarović, Bosiljka, Pilipović, Ivan, "Characterization of thymocyte phenotypic alterations induced by long-lasting beta-adrenoceptor blockade in vivo and its effects on thymocyte proliferation and apoptosis" in Molecular and Cellular Biochemistry, 285, no. 1-2 (2006):87-99,
https://doi.org/10.1007/s11010-005-9059-5 . .

TY  - JOUR
AU  - Plećaš-Solarović, Bosiljka
AU  - Pešić, Vesna
AU  - Radojević, Katarina
AU  - Leposavić, Gordana
PY  - 2006
UR  - http://intor.torlakinstitut.com/handle/123456789/206
AB  - In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3- and 18-month-old male Wistar rats and the percentages of bromodeoxyuridine-incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7-fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter-lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus-related changes in immunological aging.
PB  - Wiley, Hoboken
T2  - Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia
T1  - Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats
EP  - 386
IS  - 6
SP  - 380
VL  - 35
DO  - 10.1111/j.1439-0264.2006.00698.x
ER  - 

@article{
author = "Plećaš-Solarović, Bosiljka and Pešić, Vesna and Radojević, Katarina and Leposavić, Gordana",
year = "2006",
abstract = "In order to provide a morphometrical description of the changes in the aged rat thymus and to relate them to apoptotic and proliferative activity of thymocytes, the thymuses from 3- and 18-month-old male Wistar rats and the percentages of bromodeoxyuridine-incorporating and apoptotic cells in cultures of thymocytes were assessed by stereological analysis and flow cytometry, respectively. In old rats the volume of lymphoepithelial thymic tissue is markedly reduced, reflecting a sharp decrease in the total number of thymocytes. A reduction in the proliferative capacity of thymocytes and increase in their susceptibility to apoptosis are, most likely, primarily responsible for a 7-fold reduction in thymic cellularity in old animals. Furthermore, only the volume of cortical compartment was affected by aging, while that of medulla, despite of reduced cellularity, was not significantly altered. The loss of functional tissue in aged thymus is compensated by a substantial increase in the volume of inter-lobular connective and adipose tissue, so the thymic weight remained unaltered in old rats. These results suggest that thymus of aged Wistar rats exhibits morphological characteristics similar to those found in aged human thymus and thus may serve as an animal model for further investigations of thymus-related changes in immunological aging.",
publisher = "Wiley, Hoboken",
journal = "Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia",
title = "Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats",
pages = "386-380",
number = "6",
volume = "35",
doi = "10.1111/j.1439-0264.2006.00698.x"
}

Plećaš-Solarović, B., Pešić, V., Radojević, K.,& Leposavić, G.. (2006). Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats. in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia
Wiley, Hoboken., 35(6), 380-386.
https://doi.org/10.1111/j.1439-0264.2006.00698.x

Plećaš-Solarović B, Pešić V, Radojević K, Leposavić G. Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats. in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia. 2006;35(6):380-386.
doi:10.1111/j.1439-0264.2006.00698.x .

Plećaš-Solarović, Bosiljka, Pešić, Vesna, Radojević, Katarina, Leposavić, Gordana, "Morphometrical characteristics of age-associated changes in the thymus of old male wistar rats" in Journal of Veterinary Medicine Series C: Anatomia Histologia Embryologia, 35, no. 6 (2006):380-386,
https://doi.org/10.1111/j.1439-0264.2006.00698.x . .