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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

TY  - JOUR
AU  - Plećaš-Solarović, Bosiljka
AU  - Hristić-Živković, I.
AU  - Radojević, Katarina
AU  - Kosec, Duško
AU  - Leposavić, Gordana
PY  - 2005
UR  - http://intor.torlakinstitut.com/handle/123456789/191
AB  - In order to examine the influence of chronic alpha(1)-adrenergic receptor (alpha(1)-AR) blockade on the thymus structure and T-cell maturation, peripubertal and adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15 consecutive days. Thymic structure and phenotypic characteristics of the thymocytes were assessed by stereological and flow cytometry analysis, respectively. In immature rats, treatment with urapidil reduced the body weight gain and, affecting the volume of cortical compartment and its cellularity decreased the organ size and the total number of thymocytes compared to acre-matched saline-injected controls. The percentage of CD4+8- single positive (SP) thymocytes was decreased, while that of CD4-8+ was increased suggesting, most likely, a disregulation in final steps of the positively selected cells maturation. However alpha(1)-AR blockade in adult rats increased the thymus weight as a consequence of increase in the cortical size and cellularity. The increased percentage of most immature CD4-8- double negative (DN) cells associated with decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests a decelerated transition from DN to DP stage of T-cell development. As in immature rats, the treatment in adult rats evoked changes in the relative numbers of SP cells, but contrary to immature animals, favoring the maturation of CD4+8- over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of alpha(1)-ARs affects both the thymus structure and thymocyte differentiation, ii) these effects are age-dependent, pointing out to pharmacological manipulation of alpha(1)-AR-mediated signaling as potential means for modulation of the intrathymic T-cell maturation.
PB  - F Hernandez, Murcia
T2  - Histology and Histopathology
T1  - Chronic alpha(1)-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation
EP  - 841
IS  - 3
SP  - 833
VL  - 20
UR  - https://hdl.handle.net/21.15107/rcub_intor_191
ER  - 

@article{
author = "Plećaš-Solarović, Bosiljka and Hristić-Živković, I. and Radojević, Katarina and Kosec, Duško and Leposavić, Gordana",
year = "2005",
abstract = "In order to examine the influence of chronic alpha(1)-adrenergic receptor (alpha(1)-AR) blockade on the thymus structure and T-cell maturation, peripubertal and adult male rats were treated with urapidil (0.20 mg/kg BW/d; s.c.) over 15 consecutive days. Thymic structure and phenotypic characteristics of the thymocytes were assessed by stereological and flow cytometry analysis, respectively. In immature rats, treatment with urapidil reduced the body weight gain and, affecting the volume of cortical compartment and its cellularity decreased the organ size and the total number of thymocytes compared to acre-matched saline-injected controls. The percentage of CD4+8- single positive (SP) thymocytes was decreased, while that of CD4-8+ was increased suggesting, most likely, a disregulation in final steps of the positively selected cells maturation. However alpha(1)-AR blockade in adult rats increased the thymus weight as a consequence of increase in the cortical size and cellularity. The increased percentage of most immature CD4-8- double negative (DN) cells associated with decreased percentage of immature CD4+8+ double positive (DP) thymocytes suggests a decelerated transition from DN to DP stage of T-cell development. As in immature rats, the treatment in adult rats evoked changes in the relative numbers of SP cells, but contrary to immature animals, favoring the maturation of CD4+8- over CD4-8+ thymocytes. These results demonstrate that: i) chronic blockade of alpha(1)-ARs affects both the thymus structure and thymocyte differentiation, ii) these effects are age-dependent, pointing out to pharmacological manipulation of alpha(1)-AR-mediated signaling as potential means for modulation of the intrathymic T-cell maturation.",
publisher = "F Hernandez, Murcia",
journal = "Histology and Histopathology",
title = "Chronic alpha(1)-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation",
pages = "841-833",
number = "3",
volume = "20",
url = "https://hdl.handle.net/21.15107/rcub_intor_191"
}

Plećaš-Solarović, B., Hristić-Živković, I., Radojević, K., Kosec, D.,& Leposavić, G.. (2005). Chronic alpha(1)-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation. in Histology and Histopathology
F Hernandez, Murcia., 20(3), 833-841.
https://hdl.handle.net/21.15107/rcub_intor_191

Plećaš-Solarović B, Hristić-Živković I, Radojević K, Kosec D, Leposavić G. Chronic alpha(1)-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation. in Histology and Histopathology. 2005;20(3):833-841.
https://hdl.handle.net/21.15107/rcub_intor_191 .

Plećaš-Solarović, Bosiljka, Hristić-Živković, I., Radojević, Katarina, Kosec, Duško, Leposavić, Gordana, "Chronic alpha(1)-adrenoreceptor blockade produces age-dependent changes in rat thymus structure and thymocyte differentiation" in Histology and Histopathology, 20, no. 3 (2005):833-841,
https://hdl.handle.net/21.15107/rcub_intor_191 .

TY  - JOUR
AU  - Rauški, Aleksandra
AU  - Kosec, Duško
AU  - Vidić-Danković, Biljana
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2003
UR  - http://intor.torlakinstitut.com/handle/123456789/162
AB  - The study revealed that beta-adrenoceptor blockade with propranolol (0.40 mg/100 g/day, s.c.) in adult male DA rats: (i) increased the thymocyte proliferation and apoptosis, (ii) caused disturbances in kinetics of T cell differentiation leading to distinguishable changes in relative proportion of thymocytes at distinct maturational steps and to an expansion of the most mature single positive (CD4+, CD8+) thymocyte pool, (iii) affected the relative proportion of neither CD4+ nor CD8+ peripheral blood lymphocytes (PBL), and (iv) augmented the relative number of CD8+CD25+ cells. Thus, the results suggest the role of beta-adrenoceptors in fine-tuning of T cell maturation, and, possibly, distribution and activation of distinct PBL subsets.
PB  - Taylor & Francis Ltd, Abingdon
T2  - International Journal of Neuroscience
T1  - Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes
EP  - 1673
IS  - 12
SP  - 1653
VL  - 113
DO  - 10.1080/00207450390245216
ER  - 

@article{
author = "Rauški, Aleksandra and Kosec, Duško and Vidić-Danković, Biljana and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2003",
abstract = "The study revealed that beta-adrenoceptor blockade with propranolol (0.40 mg/100 g/day, s.c.) in adult male DA rats: (i) increased the thymocyte proliferation and apoptosis, (ii) caused disturbances in kinetics of T cell differentiation leading to distinguishable changes in relative proportion of thymocytes at distinct maturational steps and to an expansion of the most mature single positive (CD4+, CD8+) thymocyte pool, (iii) affected the relative proportion of neither CD4+ nor CD8+ peripheral blood lymphocytes (PBL), and (iv) augmented the relative number of CD8+CD25+ cells. Thus, the results suggest the role of beta-adrenoceptors in fine-tuning of T cell maturation, and, possibly, distribution and activation of distinct PBL subsets.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "International Journal of Neuroscience",
title = "Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes",
pages = "1673-1653",
number = "12",
volume = "113",
doi = "10.1080/00207450390245216"
}

Rauški, A., Kosec, D., Vidić-Danković, B., Plećaš-Solarović, B.,& Leposavić, G.. (2003). Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes. in International Journal of Neuroscience
Taylor & Francis Ltd, Abingdon., 113(12), 1653-1673.
https://doi.org/10.1080/00207450390245216

Rauški A, Kosec D, Vidić-Danković B, Plećaš-Solarović B, Leposavić G. Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes. in International Journal of Neuroscience. 2003;113(12):1653-1673.
doi:10.1080/00207450390245216 .

Rauški, Aleksandra, Kosec, Duško, Vidić-Danković, Biljana, Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Effects of beta-adrenoceptor blockade on the phenotypic characteristics of thymocytes and peripheral blood lymphocytes" in International Journal of Neuroscience, 113, no. 12 (2003):1653-1673,
https://doi.org/10.1080/00207450390245216 . .

TY  - JOUR
AU  - Rauški, Aleksandra
AU  - Kosec, Duško
AU  - Vidić-Danković, Biljana
AU  - Radojević, Katarina
AU  - Plećaš-Solarović, Bosiljka
AU  - Leposavić, Gordana
PY  - 2003
UR  - http://intor.torlakinstitut.com/handle/123456789/161
AB  - The present study was undertaken in order to further clarify putative role of the adrenergic innervation in the regulation of the intrathymic T-cell maturation. For this purpose adult male DA rats were subjected to either 4-day- or 16-day-long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte proliferative and apoptotic index, was assessed in these animals by flow cytometric analysis. Propranolol treatment, in spite of duration, increased both the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated controls). In 4-day-treated animals the thymus cellularity and thymus weight remained unaltered, while in 16-day-treated rats the values of both of these parameters were reduced (since increase in the thymocyte apoptotic index overcame that in the proliferative index). The treatments of both durations affected the thymocyte phenotypic profile in a similar pattern, but the changes were more pronounced in rats exposed to the treatment of longer duration. The relative proportion of the least mature CD4-8- double negative (DN) TCRalphabeta(-) cells was increased, those of thymocytes at distinct differentiational stages on the transitional route to the CD4+8+ double positive (DP) TCRalphabeta(low) stage decreased (all subsets of TCRalphabeta(-) in both groups of rats, and those. with low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or unaltered (all subsets of TCRalphabeta(low) cells in 4-day-treated rats). Furthermore, the percentage of CD4+8+ DP TCRalphabeta(low) cells was significantly elevated, as well as those of the most mature CD4+8-TCRalphabeta(high) and CD4-8+TCRalphabeta(high) cells (the increase in the percentage of former was much more conspicuous than that of the latter), while the relative proportion of their direct detectable precursors (CD4+8+ DP TCRalphabeta(high)) Was reduced. Thus, the present study: i) further supports notion of pharmacological manipulation of adrenergic action as an efficient means in modulation of the T-cell development, and hence T-cell-dependent immune response, and ii) provides more specific insight into T-cell maturation sequence point/s particularly sensitive to beta-adrenoceptor ligand action.
PB  - Taylor & Francis Ltd, Abingdon
T2  - Immunopharmacology and Immunotoxicology
T1  - Thymopoiesis following chronic blockade of beta-adrenoceptors
EP  - 528
IS  - 4
SP  - 513
VL  - 25
DO  - 10.1081/IPH-120026437
ER  - 

@article{
author = "Rauški, Aleksandra and Kosec, Duško and Vidić-Danković, Biljana and Radojević, Katarina and Plećaš-Solarović, Bosiljka and Leposavić, Gordana",
year = "2003",
abstract = "The present study was undertaken in order to further clarify putative role of the adrenergic innervation in the regulation of the intrathymic T-cell maturation. For this purpose adult male DA rats were subjected to either 4-day- or 16-day-long propranolol treatment (0.40 mg propranolol/100 g/day, s.c.) and the expression of CD4/8/TCRalphabeta on thymocytes, as well as thymocyte proliferative and apoptotic index, was assessed in these animals by flow cytometric analysis. Propranolol treatment, in spite of duration, increased both the thymocyte proliferative and apoptotic index (vs. respective vehicle-treated controls). In 4-day-treated animals the thymus cellularity and thymus weight remained unaltered, while in 16-day-treated rats the values of both of these parameters were reduced (since increase in the thymocyte apoptotic index overcame that in the proliferative index). The treatments of both durations affected the thymocyte phenotypic profile in a similar pattern, but the changes were more pronounced in rats exposed to the treatment of longer duration. The relative proportion of the least mature CD4-8- double negative (DN) TCRalphabeta(-) cells was increased, those of thymocytes at distinct differentiational stages on the transitional route to the CD4+8+ double positive (DP) TCRalphabeta(low) stage decreased (all subsets of TCRalphabeta(-) in both groups of rats, and those. with low expression of TCRalphabeta in rats subjected to 16-day-long treatment) or unaltered (all subsets of TCRalphabeta(low) cells in 4-day-treated rats). Furthermore, the percentage of CD4+8+ DP TCRalphabeta(low) cells was significantly elevated, as well as those of the most mature CD4+8-TCRalphabeta(high) and CD4-8+TCRalphabeta(high) cells (the increase in the percentage of former was much more conspicuous than that of the latter), while the relative proportion of their direct detectable precursors (CD4+8+ DP TCRalphabeta(high)) Was reduced. Thus, the present study: i) further supports notion of pharmacological manipulation of adrenergic action as an efficient means in modulation of the T-cell development, and hence T-cell-dependent immune response, and ii) provides more specific insight into T-cell maturation sequence point/s particularly sensitive to beta-adrenoceptor ligand action.",
publisher = "Taylor & Francis Ltd, Abingdon",
journal = "Immunopharmacology and Immunotoxicology",
title = "Thymopoiesis following chronic blockade of beta-adrenoceptors",
pages = "528-513",
number = "4",
volume = "25",
doi = "10.1081/IPH-120026437"
}

Rauški, A., Kosec, D., Vidić-Danković, B., Radojević, K., Plećaš-Solarović, B.,& Leposavić, G.. (2003). Thymopoiesis following chronic blockade of beta-adrenoceptors. in Immunopharmacology and Immunotoxicology
Taylor & Francis Ltd, Abingdon., 25(4), 513-528.
https://doi.org/10.1081/IPH-120026437

Rauški A, Kosec D, Vidić-Danković B, Radojević K, Plećaš-Solarović B, Leposavić G. Thymopoiesis following chronic blockade of beta-adrenoceptors. in Immunopharmacology and Immunotoxicology. 2003;25(4):513-528.
doi:10.1081/IPH-120026437 .

Rauški, Aleksandra, Kosec, Duško, Vidić-Danković, Biljana, Radojević, Katarina, Plećaš-Solarović, Bosiljka, Leposavić, Gordana, "Thymopoiesis following chronic blockade of beta-adrenoceptors" in Immunopharmacology and Immunotoxicology, 25, no. 4 (2003):513-528,
https://doi.org/10.1081/IPH-120026437 . .