Effects of cyclosporin A, rapamycin, and FK520 on peripheral T-cell deletion and anergy.
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-TCR alpha beta 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.
Prud'homme
G J
GJ
Department of Pathology, McGill University, Montreal, Canada.
Vanier
L E
LE
Bocarro
D C
DC
Ste-Croix
H
H
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D017635:Clonal Anergy / Q000187:drug effects; D017637:Clonal Deletion / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D011090:Polyenes / Q000494:pharmacology; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D020123:Sirolimus; D018089:Superantigens / Q000276:immunology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D016559:Tacrolimus / Q000031:analogs & derivatives / Q000494:pharmacology
D000911:Antibodies, Monoclonal; D007166:Immunosuppressive Agents; D011090:Polyenes; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; D016572:Cyclosporine; C058028:immunomycin; D020123:Sirolimus; D016559:Tacrolimus