The influence of cyclosporin A on lymphocyte attenuator expression.
B and T lymphocyte attenuator (BTLA), a recently identified immune inhibitory receptor, has been demonstrated to have the ability to maintain self-tolerance and transplant-tolerance in mice. However, little is known about the effects of immunosuppressive drugs on the expression of BTLA. In the present study, we observed that the immunosuppressive drug cyclosporin A (CsA) could significantly reduce BTLA but not CD25 and CD69 expression on CD4+ T cells during activation in vitro, while rapamycin (RPM) had little effect on it. Exogenous interleukin-2 (IL-2) failed to reverse the inhibitory effect that CsA had on BTLA expression. Furthermore, phorbol 12-myristate 13-acetate (PMA) or ionomycin alone could efficiently induce BTLA protein expression on CD4+ and CD8+ T cells, while CsA significantly suppressed BTLA expression in this system. The present data indicate that the regulation of BTLA expression on CD4+ T cells does not depend on IL-2 and T cell activation but depends on calcineurin-dependent and calcineurin-independent pathways. The observation that CsA significantly inhibits BTLA expression on CD4+ T cells during activation, suggests that CsA might block the immune tolerance induced by BTLA and potentially increase the susceptibility to autoimmune diseases and graft rejection.
Zeng
Chun
C
Transplantation Biology Research Division, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Zhen
Yu
Y
Shu
Shang-an
SA
Wu
Tinghe
T
Yi
Huanfa
H
Lian
Zhe-Xiong
ZX
Zhao
Yong
Y
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis / Q000276:immunology; D001327:Autoimmune Diseases / Q000188:drug therapy / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D016572:Cyclosporine / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000276:immunology; D006084:Graft Rejection / Q000188:drug therapy / Q000276:immunology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007376:Interleukin-2 / Q000276:immunology; D053645:Interleukin-2 Receptor alpha Subunit / Q000096:biosynthesis / Q000276:immunology; D037181:Lectins, C-Type; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology; D051379:Mice; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000276:immunology; D017634:Self Tolerance / Q000187:drug effects* / Q000276:immunology; D020123:Sirolimus / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D023001:Transplantation Tolerance / Q000187:drug effects* / Q000276:immunology; D000099192:CD69 Antigens
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D002273:Carcinogens; D016572:Cyclosporine; D007166:Immunosuppressive Agents; D007376:Interleukin-2; D053645:Interleukin-2 Receptor alpha Subunit; D037181:Lectins, C-Type; D011971:Receptors, Immunologic; D020123:Sirolimus; D013755:Tetradecanoylphorbol Acetate; D000099192:CD69 Antigens; C488868:BTLA protein, mouse