FK506 potentiates steroid-induced T-cell apoptosis.

BACKGROUND

FK506 and glucocorticoids are used for allograft rejection, graft-versus-host disease, and autoimmune diseases.

MATERIALS

We investigated the combined effect of FK506 and glucocorticoids on T-cell apoptosis.

RESULTS

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.

CONCLUSIONS

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.