Effects of Cyclosporin A, Rapamycin, and FK520 on Peripheral T-Cell Deletion and Anergy

• Published in: Cellular immunology 1995-08, Vol.164 (1), p.47-56
• Main Authors: Prud'homme, Gérald J., Vanier, Laurent E., Bocarro, Danita C., Ste-Croix, Hékéne
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Monoclonal - immunology; Antibodies, Monoclonal - pharmacology; CD4-Positive T-Lymphocytes - immunology; Clonal Anergy - drug effects; Clonal Deletion - drug effects; Cyclosporine - pharmacology; Immunosuppressive Agents - pharmacology; Mice; Mice, Inbred BALB C; Mice, Inbred DBA; Polyenes - pharmacology; Receptors, Antigen, T-Cell, alpha-beta - immunology; Sirolimus; Superantigens - immunology; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; Tacrolimus - analogs & derivatives; Tacrolimus - pharmacology
• ISSN: 0008-8749; 1090-2163
• DOI: 10.1006/cimm.1995.1141

In this study we compare the effects of cyclosporin A (CsA), FK520 (an agent similar to FK506), and rapamycin (RAPA) on peripheral T-cell deletion induced by either superantigens or anti-TCRαβ mAb, and on anergy induced by superantigens in mice. CsA enhanced T-cell deletion and blocked anergy induction (in residual T cells), while FK520 and RAPA had no effects on these processes. CsA also enhanced apoptosis of stimulated T cells in vitro, where cell death occurred without prior proliferation and in the absence of phagocytes. Our data suggest that CsA exerts these effects through a calcineurin-independent pathway, and this may be relevant to the development of tolerance in some models.