FK506 INHIBITS ANTIGEN RECEPTOR-MEDIATED INDUCTION OF C-REL IN B-LYMPHOID AND T-LYMPHOID CELLS

Stimulation of B and T cells via the antigen receptor, by phorbol este r or by phorbol ester and ionomycin, leads to nuclear translocation of the inducible transcription factor NF-kappa B, comprising the p50 and p65 rel-related polypeptides. In this report we show that c-rel is a component of the antigen receptor-induced kappa B binding proteins in both B and T cells. Whereas NF-kappa B can be induced by phorbol ester alone, optimal induction of c-rel requires stimulation by both phorbo l ester and ionomycin, the dual signal that is necessary for prolifera tion of untransformed lymphocytes. Furthermore, c-rel induction is blo cked by the immunosuppressive drug FK506 that is known to inhibit B an d T cell activation. c-rel-dependent transactivation of the interleuki n-2 receptor alpha chain (IL-2R alpha) promoter is augmented by coexpr ession of calcineurin, suggesting the involvement of a calcineurin-dep endent intracellular pathway. Our results identify c-rel as a target o f immunosuppressive agents and illustrate the similarity of activation pathways in both B and T cells.