EFFECTS OF CYCLOSPORINE-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 FR506), and rapamycin (RAPA) on peripheral T-cell de letion induced by either superantigens or anti-TCR alpha beta mAb, and on anergy induced by superantigens in mice. CsA enhanced T-cell delet ion and blocked anergy induction (in residual T cells), while FK520 an d RAPA had no effects on these processes. CsA also enhanced apoptosis of stimulated T cells in vitro, where cell death occurred without prio r proliferation and in the absence of phagocytes. Our data suggest tha t CsA exerts these effects through a calcineurin-independent pathway, and this may be relevant to the development of tolerance in some model s. (C) 1995 Academic Press, Inc.