Effects of FK506 on T cell apoptosis.

FK506 is an immunosuppressive drug that inhibits T cell receptor (TCR) -mediated signal transduction. This drug can induce immunological tolerance in allograft recipients. We investigated the effects of FK506 on T cell apoptosis induction.Staphylococcal enterotoxin B (SEB) injection in mice resulted in splenic T cell apoptosis. FK506 augmented this SEB-induced peripheral T cell apoptosis. Also, profound reduction of SEB-reactive CD4+Vβ8+T cells was observed in SEBFK506-treated mice.Similary, pretreatment with FK506 significantly augmented thymocyte DNA fragmentation induced by dexamethasone (DEX) injection. Increased thymic apoptosis resulted in the reduction of thymocytes after FK506/DEX injection. Similary, FK506 synergistically enhanced DEX-mediated apoptosis of human peripheral blood T cells in vitro.Apoptosis is required for the generation and maintenance of self-tolerance in the immune system. These findings suggest that FK506-triggered apoptosis following elimination of T cells may represent a potential mechanism of the immunological tolerance achieved by FK506 treatment.