Abstract
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.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / immunology
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Antibodies, Monoclonal / pharmacology
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CD4-Positive T-Lymphocytes / immunology
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Clonal Anergy / drug effects
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Clonal Deletion / drug effects
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Cyclosporine / pharmacology
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Immunosuppressive Agents / pharmacology*
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Mice
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Mice, Inbred BALB C
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Mice, Inbred DBA
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Polyenes / pharmacology
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Receptors, Antigen, T-Cell, alpha-beta / immunology
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Sirolimus
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Superantigens / immunology
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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Tacrolimus / analogs & derivatives
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Tacrolimus / pharmacology
Substances
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Antibodies, Monoclonal
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Immunosuppressive Agents
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Polyenes
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Receptors, Antigen, T-Cell, alpha-beta
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Superantigens
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Cyclosporine
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immunomycin
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Sirolimus
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Tacrolimus