Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes.
One mechanism by which the immune system develops the ability to discriminate self from nonself is the deletion of autoreactive T-cell clones during thymic maturation. The drug cyclosporin A (CsA) has been shown to interfere with this process, allowing the escape of normally 'forbidden' T-cell clones and the appearance of autoimmune disease. Recently, it has been demonstrated that immature thymocytes undergo programmed cell death (apoptosis) upon activation via the T-cell receptor. A similar phenomenon of activation-induced cell death (AICD) has been observed in T-cell hybridomas. Here we show that AICD in T-cell hybridomas in vitro and in thymocytes in vivo is blocked by CsA. Thus, clonal deletion may involve AICD when self-reactive, immature T cells are induced by self antigen, and CsA may cause autoimmunity by interfering with this process.
Shi
Y F
YF
Department of Immunology, University of Alberta, Edmonton, Canada.
Sahai
B M
BM
Green
D R
DR
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D002470:Cell Survival / Q000187:drug effects*; D003524:Cyclosporins / Q000494:pharmacology*; D004249:DNA Damage; D006825:Hybridomas; D007108:Immune Tolerance; D051379:Mice; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology*
D000945:Antigens, Differentiation, T-Lymphocyte; D003524:Cyclosporins