Analysis of cell surface antigens on glucocorticoid-treated rat thymocytes with monoclonal antibodies

Tsuchida, Masahiro; Konishi, M; Jojima, Kazutaka; Naito, Katsusuke; Fujikura, Yoshihisa; Fukumoto, Tetsuo

doi:10.1016/0165-2478(94)90160-0

Cited by 26 publications

(12 citation statements)

References 21 publications

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“…These findings are in accordance with data indicating that estrogens regulate transition from the DN to the DP stage of thymocyte development, as well as the size of the DP subset [17,54]. The reduced percentage of CD4+8-TCR·ß -/TCR·ß low cells, which are shown to be direct precursors of CD4+8+TCR·ß low cells [36], seems to be consistent with the previous assumption. However, the increased percentage of CD4+8+TCR·ß low cells, which are believed to be the cells that enter selection processes, viewed in light of unaltered relative numbers of CD4+8+TCR·ß high thymocytes, which are assumed to be the cells that just passed positive selection [30], may reflect, at least partly, a decreased/decelerated positive selection of thymocytes.…”

Section: Discussionsupporting

confidence: 82%

“…It has been shown that thymocytes display a triphasic distribution of R73 staining, and therefore three distinct subsets can be distinguished: (a) high level of TCR·ß expression (TCR·ß high ); (b) a lower but clearly measurable level of antigen expression (TCR·ß low ), and (c) absence of measurable R73 binding and staining (TCR·ß -) [36]. With respect to the expression of CD4 and CD8 molecules, the level of TCR·ß expression and twelve subsets of thymocytes were delineated [36].…”

Section: Analysis Of Cd4/cd8/tcr·ß Expressionmentioning

confidence: 99%

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Neonatal Androgenization Affects the Intrathymic T-Cell Maturation in Rats

Leposavić

Pejčić-Karapetrović

Kosec

2005

Neuroimmunomodulation

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The thymus structure, expression of CD4/CD8/TCRαβ on thymocytes and thymocyte proliferative and apoptotic indexes were analyzed in sexually immature 30-day-old and in sexually mature 60-day-old female rats neonatally androgenized (NA) by subcutaneous injection of 500 µg testosterone propionate/day on days 1–3 and in their vehicle-administered counterparts. The treatment affected normal thymus development. Thus, at 30 days of age, there was a reduction in the thymus weight, reflecting a decrease in the main thymic compartments. However, at 60 days of age, thymus weight did not significantly differ from that in age-matched controls, since the cortical volume enlargement was followed by a proportional decrease in the medullary volume. In rats of both ages, the changes in thymic compartments most likely reflected alterations in the size of both lymphoid and nonlymphoid components. Furthermore, in NA rats, substantial changes in thymocyte phenotypic characteristics were registered, in spite of their age. In both groups of NA rats, a decrease in the relative proportion of the least mature CD4–8–TCRαβ– cells and in that of CD4+8– TCRαβ–/TCRαβ^low cells followed by an increase in the percentage of their successor CD4+8+TCRαβ–/TCRαβ^low cells was detected. In addition, in 30-day-old NA rats, the relative proportions of CD4+8+TCRαβ^high cells (just positively selected) and that of mature single positive (CD4+8– and CD4–8+) and CD4–8– double negative TCRαβ^high cells, were reduced, while in 60-day-old NA rats only the percentage of CD4+8+TCRαβ^high thymocytes was decreased. Thus, the study showed that the changes in the development of the hypothalamo-pituitary-gonadal axis induced by neonatal androgenization may affect the thymus development and intrathymic T-cell maturation.

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Section: Discussionsupporting

confidence: 82%

Section: Analysis Of Cd4/cd8/tcr·ß Expressionmentioning

confidence: 99%

Neonatal Androgenization Affects the Intrathymic T-Cell Maturation in Rats

Leposavić

Pejčić-Karapetrović

Kosec

2005

Neuroimmunomodulation

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“…It has been shown that thymocytes display a triphasic distribution of R73 staining, thus that three distinct subsets characterized by: (a) high level of TCR α β expression (TCR α β high ); (b) lower, but clearly measurable level of antigen expression (TCR α β low ) and (c) absence of measurable R73 binding and staining (TCR α β − ) can be distinguished. In respect to the expression of CD4 and CD8 molecules, on one side, and the level of TCR α β expression, on the other side, twelve subsets of thymocytes were delineated 27 …”

Section: Effect Of Gnrh‐a Treatment In Ovx Ratsmentioning

confidence: 99%

Gonadotropin‐releasing Hormone Agonist Administration Affects the Thymopoiesis in Adult Female Rats Independently on Gonadal Hormone Production

Leposavić

Pekić

Kosec

2005

American J Rep Immunol

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“…In rats or mice, FK506 has been shown to cause a dramatic elimination of phenotypically mature T cells in the thymus, reflected histologically by a selective atrophy of the thymic medulla [138][139][140]. In rats or mice, FK506 has been shown to cause a dramatic elimination of phenotypically mature T cells in the thymus, reflected histologically by a selective atrophy of the thymic medulla [138][139][140].…”

Section: Disruption Of Intrathymic T Cell Development By Fk506mentioning

confidence: 99%

Preface

Choudhary

2000

CMC

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The macrolactam natural product, FK506 (Tacrolimus), acts as apowerful and clinically useful immnosuppressant through disruption ofsignaling events mediated by the calciumdependent serine/threonineprotein phosphatase, calcineurin (CaN), in T lymphocytes. Its mechanism of action involves the formation of a molecular complex with the intracellula FK506binding protein-12 (FKBP12), thereby acquiring the ability to interactwith CaN and to interfere w i t h i t s a c c e s s t o a n d d e p h o s p h o r y l a t i o n o f v a r i o u s s u b s t r a t e s . A m o n g the CaN substrates whose activity is altered by FK506, the nuclear factors of activated T cells (NFAT), a family of transcription factors regulating lymphokine gene expression, have been shown to play a prominent role in FK506-induced immunosuppression. Over the past few years, additional members of the FKBP and NFAT families of proteins have been identified, providing further insights into the complexity of FK506 biological effects. Furthermore, it has become clear that, predominantly as a result of CaN inhibition, FK506 alters multiple biochemical processes in a variety of cells besides lymphocytes. This may account for the adverse side effects of the drug, including neurotoxicity and nephrotoxicity. Extensive medicinal chemistry efforts have been devoted to the generation of analogs of FK506 with the hope of identifying compounds with an improved therapeutic index, that could have broader therapeutic utility than the parent drug. These efforts yielded several compounds with unique biochemical attributes, showing evidence for a dissociation between immunosuppressive and toxic properties, which may pave the way towards designing safer FK506-related immunosuppressants.

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Analysis of cell surface antigens on glucocorticoid-treated rat thymocytes with monoclonal antibodies

Cited by 26 publications

References 21 publications

Neonatal Androgenization Affects the Intrathymic T-Cell Maturation in Rats

Neonatal Androgenization Affects the Intrathymic T-Cell Maturation in Rats

Gonadotropin‐releasing Hormone Agonist Administration Affects the Thymopoiesis in Adult Female Rats Independently on Gonadal Hormone Production

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