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.
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.
Authors: Dana E Orange; Nathalie E Blachere; John Fak; Salina Parveen; Mayu O Frank; Margo Herre; Suyan Tian; Sebastien Monette; Robert B Darnell Journal: Elife Date: 2013-02-05 Impact factor: 8.140