Migita K, Eguchi K, Kawabe Y, Origuchi T, Tominaga M, Nagataki S
First Department of Internal Medicine, Nagasaki University School of Medicine, Sakamoto, Japan.
Transplantation. 1997 Nov 15;64(9):1365-9. doi: 10.1097/00007890-199711150-00022.
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.
FK506和糖皮质激素用于同种异体移植排斥反应、移植物抗宿主病及自身免疫性疾病。
我们研究了FK506和糖皮质激素对T细胞凋亡的联合作用。
给小鼠注射地塞米松通过增加DNA片段化减少了CD4+CD8+胸腺细胞的数量。用FK506预处理显著增强了地塞米松注射诱导的胸腺细胞DNA片段化。FK506/地塞米松注射后胸腺细胞凋亡增加导致CD4+CD8+胸腺细胞消失。除胸腺细胞外，成熟的人外周血T细胞在体外暴露于地塞米松时会发生凋亡。FK506协同增强地塞米松介导的人外周血T细胞凋亡。
因此，我们的结果表明FK506在体内和体外均增强了地塞米松诱导的T细胞凋亡。这种相互作用可能增强这两种药物实现的治疗性免疫抑制作用。
