Dual effect of glucocorticoids on apoptosis of human autoreactive and foreign antigen-specific T cells

The efficacy of glucocorticoids in the treatment of multiple sclerosis may involve the induction of T cell apoptosis. Here, we report that glucocortic oids have two different effects on the vulnerability of human antigen-speci fic T cells: (i) steroids induce T cell apoptosis in a CD95-independent, bu t caspase-dependent manner; (ii) steroids protect T cells from CD95-mediate d apoptosis which, however, is also caspase-dependent. An increase in BCL-2 expression is observed upon incubation with steroids. Thus, inhibition of CD95-mediated T cell apoptosis may be an undesirable side-effect resulting in survival of activated T cells and the maintenance of pathogenic immune r esponses might explain the lack of long-term glucocorticoid therapy. (C) 20 00 Elsevier Science B.V. All rights reserved.