FK506 POTENTIATES STEROID-INDUCED T-CELL APOPTOSIS1

Publisher Website
Google Scholar
Abstract
FK506 and glucocorticoids are used for allograft rejection, graft-versus-host disease, and autoimmune diseases. We investigated the combined effect of FK506 and glucocorticoids on T-cell apoptosis. Dexamethasone injection in mice reduced the number of CD4+CD8+thymocytes by increasing DNA fragmentation. Pretreatment with FK506 significantly augmented thymocyte DNA fragmentation induced by dexamethasone injection. Increased thymic apoptosis resulted in the disappearance of CD4+CD8+thymocytes, after FK506/dexamethasone injection. In addition to thymocytes, mature human peripheral blood T cells undergo apoptosis by exposure to dexamethasone in vitro. FK506 synergistically enhanced dexamethasone-mediated apoptosis of human peripheral blood T cells. Thus, our results showed that FK506 enhanced dexamethasone-induced apoptosis of T cells in vivo and in vitro. This interaction may enhance the therapeutic immunosuppression achieved by these two drugs.