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  - Perišić, Milica
AU  - Bufan, Biljana
AU  - Stojić-Vukanić, Zorica
AU  - Pilipović, Ivan
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2013
UR  - http://intor.torlakinstitut.com/handle/123456789/377
AB  - The study was undertaken to assess the effects of ovarian hormone withdrawal in prepubertal age on thymopoiesis in 2- (young) and 11-month-old (middle-aged) rats. In ovariectomized (Ox) rats, irrespective of age, thymic weight and cellularity were greater than in age-matched controls, but the values of both parameters exhibited the age-related decline. In addition, although thymopoietic efficiency was increased in both groups of Ox rats when compared with age-matched controls, thymopoiesis exhibited the age-related decline mirrored in the lower numbers of both CD4+ and CD8+ recent thymic emigrants in peripheral blood. This reflected the prethymic changes affecting bone marrow progenitor generation/entry and the thymic alterations encompassing the impaired progenitor progression through early pre-T-cell receptor developmental stages (defined by CD45RC/CD2 expression) and, possibly, a more pronounced decrease in the proliferation of the most mature thymocytes. Apart from the changes at thymocyte level, in Ox rats the age-related alterations in thymic stroma (substantiated in a prominent loss of thymic epithelial cells) were registered. Ovariectomy-induced changes in thymic lymphoid and epithelial component, most probably, influenced each other leading to the increase in thymic expression of interleukin-6 and interleukin-7 mRNAs along with time after ovariectomy. Collectively, the study showed that the withdrawal of ovarian hormones in prepubertal age increases the efficiency of thymopoiesis in young adult rats, but does not prevent decline in thymopoiesis occurring with age.
PB  - Royal Soc Medicine Press Ltd, London
T2  - Experimental Biology and Medicine
T1  - Ovarian hormone withdrawal in prepubertal developmental stage does not prevent thymic involution in rats
EP  - 657
IS  - 6
SP  - 641
VL  - 238
DO  - 10.1177/1535370213489475
ER  - 

@article{
author = "Arsenović-Ranin, Nevena and Perišić, Milica and Bufan, Biljana and Stojić-Vukanić, Zorica and Pilipović, Ivan and Kosec, Duško and Leposavić, Gordana",
year = "2013",
abstract = "The study was undertaken to assess the effects of ovarian hormone withdrawal in prepubertal age on thymopoiesis in 2- (young) and 11-month-old (middle-aged) rats. In ovariectomized (Ox) rats, irrespective of age, thymic weight and cellularity were greater than in age-matched controls, but the values of both parameters exhibited the age-related decline. In addition, although thymopoietic efficiency was increased in both groups of Ox rats when compared with age-matched controls, thymopoiesis exhibited the age-related decline mirrored in the lower numbers of both CD4+ and CD8+ recent thymic emigrants in peripheral blood. This reflected the prethymic changes affecting bone marrow progenitor generation/entry and the thymic alterations encompassing the impaired progenitor progression through early pre-T-cell receptor developmental stages (defined by CD45RC/CD2 expression) and, possibly, a more pronounced decrease in the proliferation of the most mature thymocytes. Apart from the changes at thymocyte level, in Ox rats the age-related alterations in thymic stroma (substantiated in a prominent loss of thymic epithelial cells) were registered. Ovariectomy-induced changes in thymic lymphoid and epithelial component, most probably, influenced each other leading to the increase in thymic expression of interleukin-6 and interleukin-7 mRNAs along with time after ovariectomy. Collectively, the study showed that the withdrawal of ovarian hormones in prepubertal age increases the efficiency of thymopoiesis in young adult rats, but does not prevent decline in thymopoiesis occurring with age.",
publisher = "Royal Soc Medicine Press Ltd, London",
journal = "Experimental Biology and Medicine",
title = "Ovarian hormone withdrawal in prepubertal developmental stage does not prevent thymic involution in rats",
pages = "657-641",
number = "6",
volume = "238",
doi = "10.1177/1535370213489475"
}

Arsenović-Ranin, N., Perišić, M., Bufan, B., Stojić-Vukanić, Z., Pilipović, I., Kosec, D.,& Leposavić, G.. (2013). Ovarian hormone withdrawal in prepubertal developmental stage does not prevent thymic involution in rats. in Experimental Biology and Medicine
Royal Soc Medicine Press Ltd, London., 238(6), 641-657.
https://doi.org/10.1177/1535370213489475

Arsenović-Ranin N, Perišić M, Bufan B, Stojić-Vukanić Z, Pilipović I, Kosec D, Leposavić G. Ovarian hormone withdrawal in prepubertal developmental stage does not prevent thymic involution in rats. in Experimental Biology and Medicine. 2013;238(6):641-657.
doi:10.1177/1535370213489475 .

Arsenović-Ranin, Nevena, Perišić, Milica, Bufan, Biljana, Stojić-Vukanić, Zorica, Pilipović, Ivan, Kosec, Duško, Leposavić, Gordana, "Ovarian hormone withdrawal in prepubertal developmental stage does not prevent thymic involution in rats" in Experimental Biology and Medicine, 238, no. 6 (2013):641-657,
https://doi.org/10.1177/1535370213489475 . .

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

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

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

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

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

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
AU  - Pilipović, Ivan
PY  - 2012
UR  - http://intor.torlakinstitut.com/handle/123456789/360
AB  - There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually diergic changes in thymopoietic efficiency, which in rodents occur around puberty and lead to a substantial phenotypic and functional remodeling of the peripheral T-cell compartment. This in turn leads to an alteration in the susceptibility to infection and various immunologically mediated pathologies. Our laboratory has explored interdependence in the programming and development of the hypothalamo-pituitary-gonadal axis and thymus using experimental model of neonatal androgenization. We have outlined critical points in the complex process of T-cell development depending on neonatal androgen imprinting and the peripheral outcome of these changes and have pointed to underlying mechanisms. Our research has particularly contributed to an understanding of the putative role of changes in catecholamine-mediated communications in the thymopoietic alterations in adult neonatally androgenized rats.
PB  - Humana Press Inc, Totowa
T2  - Immunologic Research
T1  - Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis
EP  - 19
IS  - 1-2
SP  - 7
VL  - 52
DO  - 10.1007/s12026-012-8278-6
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica and Pilipović, Ivan",
year = "2012",
abstract = "There is a growing body of evidence indicating the important role of the neonatal steroid milieu in programming sexually diergic changes in thymopoietic efficiency, which in rodents occur around puberty and lead to a substantial phenotypic and functional remodeling of the peripheral T-cell compartment. This in turn leads to an alteration in the susceptibility to infection and various immunologically mediated pathologies. Our laboratory has explored interdependence in the programming and development of the hypothalamo-pituitary-gonadal axis and thymus using experimental model of neonatal androgenization. We have outlined critical points in the complex process of T-cell development depending on neonatal androgen imprinting and the peripheral outcome of these changes and have pointed to underlying mechanisms. Our research has particularly contributed to an understanding of the putative role of changes in catecholamine-mediated communications in the thymopoietic alterations in adult neonatally androgenized rats.",
publisher = "Humana Press Inc, Totowa",
journal = "Immunologic Research",
title = "Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis",
pages = "19-7",
number = "1-2",
volume = "52",
doi = "10.1007/s12026-012-8278-6"
}

Leposavić, G., Perišić, M.,& Pilipović, I.. (2012). Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis. in Immunologic Research
Humana Press Inc, Totowa., 52(1-2), 7-19.
https://doi.org/10.1007/s12026-012-8278-6

Leposavić G, Perišić M, Pilipović I. Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis. in Immunologic Research. 2012;52(1-2):7-19.
doi:10.1007/s12026-012-8278-6 .

Leposavić, Gordana, Perišić, Milica, Pilipović, Ivan, "Role of gonadal hormones in programming developmental changes in thymopoietic efficiency and sexual diergism in thymopoiesis" in Immunologic Research, 52, no. 1-2 (2012):7-19,
https://doi.org/10.1007/s12026-012-8278-6 . .

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

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

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

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

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

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Todorović, Vera
AU  - Nikolić, I.
AU  - Perišić, Milica
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/337
AB  - The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall's corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans.
PB  - Srpsko biološko društvo, Beograd, i dr.
T2  - Archives of Biological Sciences
T1  - Immunoreactive neuropeptides in the cells of human thymus
EP  - 977
IS  - 4
SP  - 971
VL  - 63
DO  - 10.2298/ABS1104971L
ER  - 

@article{
author = "Leposavić, Gordana and Todorović, Vera and Nikolić, I. and Perišić, Milica",
year = "2011",
abstract = "The study was designed to explore the expression of different neuropeptides, viz. vasoactive intestinal peptide (VIP), calcitonin gene related peptide (CGRP), substance P (SP), bombesin and motilin in the cells of fetal and adult human thymus. Immunohistochemical staining revealed that cortical and medullary thymocytes were labeled by all antibodies, except those specific for motilin. Immunoreactive VIP and SP were observed in the solitary epithelial cells located in the subcapsular/subtrabecular cortex, at the corticomedullary junction and in the medulla. The cells within the subcapsular/subtrabecular monolayer, rare solitary cells in the deep cortex and epithelial cell network in the medulla, were labeled with antibodies to CGRP and bombesin. Hassall's corpuscles were labeled with all antibodies except that specific for SP. The obtained data obtained testify to the expression of different neuropeptides in human thymic lymphoid and non-lymphoid cells and suggest a role for neuroendocrine hormone-mediated mechanisms in the regulation of thymic homeostasis in humans.",
publisher = "Srpsko biološko društvo, Beograd, i dr.",
journal = "Archives of Biological Sciences",
title = "Immunoreactive neuropeptides in the cells of human thymus",
pages = "977-971",
number = "4",
volume = "63",
doi = "10.2298/ABS1104971L"
}

Leposavić, G., Todorović, V., Nikolić, I.,& Perišić, M.. (2011). Immunoreactive neuropeptides in the cells of human thymus. in Archives of Biological Sciences
Srpsko biološko društvo, Beograd, i dr.., 63(4), 971-977.
https://doi.org/10.2298/ABS1104971L

Leposavić G, Todorović V, Nikolić I, Perišić M. Immunoreactive neuropeptides in the cells of human thymus. in Archives of Biological Sciences. 2011;63(4):971-977.
doi:10.2298/ABS1104971L .

Leposavić, Gordana, Todorović, Vera, Nikolić, I., Perišić, Milica, "Immunoreactive neuropeptides in the cells of human thymus" in Archives of Biological Sciences, 63, no. 4 (2011):971-977,
https://doi.org/10.2298/ABS1104971L . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Perišić, Milica
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/317
AB  - The thymus plays a critical role in establishing and maintaining the peripheral T-cell pool. It does so by providing a microenvironment within which T-cell precursors differentiate and undergo selection processes to create a functional population of major histocompatibility complex-restricted, self-tolerant T cells. These cells are central to adaptive immunity. Thymic T-cell development is influenced by locally produced soluble factors and cell-to-cell interactions, as well as by sympathetic noradrenergic and endocrine system signalling. Thymic lymphoid and non-lymphoid cells have been shown not only to express beta- and alpha(1)-adrenoceptors (ARs), but also to synthesize catecholamines (CAs). Thus, it is suggested that CAs influence T-cell development via both neurocrine/endocrine and autocrine/paracrine action, and that they serve as immunotransmitters between thymocytes and nerves. CAs acting at multiple sites along the thymocyte developmental route affect T-cell generation not only numerically, but also qualitatively. Thymic CA level and synthesis, as well as AR expression exhibit sex steroid-mediated sexual dimorphism. Moreover, the influence of CAs on T-cell development exhibits glucocorticoid-dependent plasticity. This review summarizes recent findings in this field and our current understanding of complex and multifaceted neuroendocrine-immune communications at thymic level.
PB  - Czech Academy of Sciences, Institute of Physiology
T2  - Physiological Research
T1  - Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity
EP  - S82
IS  - SUPPL.1
SP  - S71
VL  - 60
DO  - 10.33549/physiolres.932175
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Perišić, Milica",
year = "2011",
abstract = "The thymus plays a critical role in establishing and maintaining the peripheral T-cell pool. It does so by providing a microenvironment within which T-cell precursors differentiate and undergo selection processes to create a functional population of major histocompatibility complex-restricted, self-tolerant T cells. These cells are central to adaptive immunity. Thymic T-cell development is influenced by locally produced soluble factors and cell-to-cell interactions, as well as by sympathetic noradrenergic and endocrine system signalling. Thymic lymphoid and non-lymphoid cells have been shown not only to express beta- and alpha(1)-adrenoceptors (ARs), but also to synthesize catecholamines (CAs). Thus, it is suggested that CAs influence T-cell development via both neurocrine/endocrine and autocrine/paracrine action, and that they serve as immunotransmitters between thymocytes and nerves. CAs acting at multiple sites along the thymocyte developmental route affect T-cell generation not only numerically, but also qualitatively. Thymic CA level and synthesis, as well as AR expression exhibit sex steroid-mediated sexual dimorphism. Moreover, the influence of CAs on T-cell development exhibits glucocorticoid-dependent plasticity. This review summarizes recent findings in this field and our current understanding of complex and multifaceted neuroendocrine-immune communications at thymic level.",
publisher = "Czech Academy of Sciences, Institute of Physiology",
journal = "Physiological Research",
title = "Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity",
pages = "S82-S71",
number = "SUPPL.1",
volume = "60",
doi = "10.33549/physiolres.932175"
}

Leposavić, G., Pilipović, I.,& Perišić, M.. (2011). Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity. in Physiological Research
Czech Academy of Sciences, Institute of Physiology., 60(SUPPL.1), S71-S82.
https://doi.org/10.33549/physiolres.932175

Leposavić G, Pilipović I, Perišić M. Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity. in Physiological Research. 2011;60(SUPPL.1):S71-S82.
doi:10.33549/physiolres.932175 .

Leposavić, Gordana, Pilipović, Ivan, Perišić, Milica, "Cellular and Nerve Fibre Catecholaminergic Thymic Network: Steroid Hormone Dependent Activity" in Physiological Research, 60, no. SUPPL.1 (2011):S71-S82,
https://doi.org/10.33549/physiolres.932175 . .

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Pilipović, Ivan
AU  - Perišić, Milica
PY  - 2011
UR  - http://intor.torlakinstitut.com/handle/123456789/328
AB  - Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naive T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via beta(2)- and alpha(1)-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of beta(2)- and alpha(1)-AR-expressing thymic nonlymphoid cells and the alpha(1)-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving alpha(1)-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naive T cell output. Copyright (C) 2011 S. Karger AG, Basel
PB  - Karger, Basel
T2  - Neuroimmunomodulation
T1  - Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity
EP  - 308
IS  - 5
SP  - 290
VL  - 18
DO  - 10.1159/000329499
ER  - 

@article{
author = "Leposavić, Gordana and Pilipović, Ivan and Perišić, Milica",
year = "2011",
abstract = "Ageing is associated with a progressive decline in thymic cytoarchitecture followed by a less efficient T cell development and decreased emigration of naive T cells to the periphery. These thymic changes are linked to increased morbidity and mortality from infectious, malignant and autoimmune diseases in old age. Therefore, it is of paramount importance to understand the thymic homeostatic processes across the life span, as well as to identify factors and elucidate mechanisms driving or contributing to the thymic involution. Catecholamines (CAs) derived from sympathetic nerves and produced locally by thymic cells represent an important component of the thymic microenvironment. In young rats, they provide a subtle tonic suppressive influence on T cell development acting via beta(2)- and alpha(1)-adrenoceptors (ARs) expressed on thymic nonlymphoid cells and thymocytes. In the face of thymic involution, a progressive increase in the thymic noradrenaline level, reflecting a rise in the density of noradrenergic nerve fibers and CA-synthesizing cells, occurs. In addition, the density of beta(2)- and alpha(1)-AR-expressing thymic nonlymphoid cells and the alpha(1)-AR thymocyte surface density also exhibit a pronounced increase with age. The data obtained from studies investigating effects of AR blockade on T cell development indicated that age-related changes in CA-mediated thymic communications, certainly those involving alpha(1)-ARs, may contribute to diminished thymopoietic efficiency in the elderly. Having in mind thymic plasticity in the course of ageing, and broadening possibilities for pharmacological modulation of CA signaling, we here present and discuss the progress in research related to a role of CAs in thymic homeostasis and age-related decay in the thymic naive T cell output. Copyright (C) 2011 S. Karger AG, Basel",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity",
pages = "308-290",
number = "5",
volume = "18",
doi = "10.1159/000329499"
}

Leposavić, G., Pilipović, I.,& Perišić, M.. (2011). Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity. in Neuroimmunomodulation
Karger, Basel., 18(5), 290-308.
https://doi.org/10.1159/000329499

Leposavić G, Pilipović I, Perišić M. Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity. in Neuroimmunomodulation. 2011;18(5):290-308.
doi:10.1159/000329499 .

Leposavić, Gordana, Pilipović, Ivan, Perišić, Milica, "Age-Associated Remodeling of Neural and Nonneural Thymic Catecholaminergic Network Affects Thymopoietic Productivity" in Neuroimmunomodulation, 18, no. 5 (2011):290-308,
https://doi.org/10.1159/000329499 . .

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Leposavić, Gordana
AU  - Perišić, Milica
PY  - 2008
UR  - http://intor.torlakinstitut.com/handle/123456789/268
AB  - The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered. Copyright (C) 2008 S. Karger AG, Basel
PB  - Karger, Basel
T2  - Neuroimmunomodulation
T1  - Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines
EP  - 322
IS  - 4-6
SP  - 290
VL  - 15
DO  - 10.1159/000156473
ER  - 

@article{
author = "Leposavić, Gordana and Perišić, Milica",
year = "2008",
abstract = "The present review summarizes recent data on age-related thymic changes termed thymic involution, and highlights the putative role of perturbances in extrathymical and, possibly, intrathymical production of gonadal steroids and catecholamines in this process. Thymic involution has been envisaged as an extremely complex process involving multifactorial mechanisms along the bone marrow-thymic axis that accounts for the major manifestations of immunosenescence. These mechanisms include basic cell aging processes (for example, cell replication and programmed cell death) and processes unique to the immune system (such as generation of the T cell receptor repertoire and control of potentially autoreactive cells). Given that the onset of age-associated thymic involution coincides with the rise in gonadal steroid levels at puberty, a causal link between these events has been suggested. It has been shown that: (1) peripubertal gonadectomy causes substantial decrease in the level of noradrenaline in adult male and female thymus and (2) catecholamines, acting via alpha- and beta-adrenoceptor, produce suppressive effects on the thymic cellularity and production of both effector and regulatory T cells. Furthermore, the possibility that gonadal steroids contribute to thymic involution is discussed in this paper. In light of recent data indicating that effects of gonadal hormone deprivation on the thymic cellularity and function are long lasting but transitory, a putative role for the intrathymic sex steroid/catecholamine production in assuring the organ involution, under conditions of their limited supply by extrathymic sources, is also considered. Copyright (C) 2008 S. Karger AG, Basel",
publisher = "Karger, Basel",
journal = "Neuroimmunomodulation",
title = "Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines",
pages = "322-290",
number = "4-6",
volume = "15",
doi = "10.1159/000156473"
}

Leposavić, G.,& Perišić, M.. (2008). Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines. in Neuroimmunomodulation
Karger, Basel., 15(4-6), 290-322.
https://doi.org/10.1159/000156473

Leposavić G, Perišić M. Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines. in Neuroimmunomodulation. 2008;15(4-6):290-322.
doi:10.1159/000156473 .

Leposavić, Gordana, Perišić, Milica, "Age-Associated Remodeling of Thymopoiesis: Role for Gonadal Hormones and Catecholamines" in Neuroimmunomodulation, 15, no. 4-6 (2008):290-322,
https://doi.org/10.1159/000156473 . .

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 . .