Cyclosporin A inhibits activation-induced cell death in T-cell hybridomas and thymocytes

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Abstract
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 maturation1–4. The drug cyclosporin A (CsA) has been shown to interfere with this process, allowing the escape of normally 'forbidden' T-cell clones5,6 and the appearance of autoimmune disease7–10. Recently, it has been demonstrated that immature thymocytes undergo programmed cell death (apoptosis) upon activation via the T-cell receptor11. A similar phenomenon of activation-induced cell death (AICD) has been observed in T-cell hybridomas12,13. 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.