心胸腺联合移植结合胸腺内注射供体胸腺细胞诱导大鼠同种异体心脏移植免疫耐受

Immune tolerance induced by combined heart-thymus transplantation with intrathymic inoculation of thymocytes in rats

目的:研究供体胸腺细胞经胸腺注射对大鼠心脏及胸腺移植的影响。方法:将SD大鼠的胸腺细胞注入W istar大鼠胸腺内,2周后行心脏及心胸腺联合移植(SD→W istar),观察移植心存活时间和病理排斥反应,检测血中及移植心中IL-2及IL-4水平。结果:单纯心脏移植及心胸腺联合移植在环孢素短期(7 d及14 d)应用下,可延长移植心及胸腺的存活时间,但不能诱导耐受;经胸腺注射供体胸腺细胞后,行单纯心脏移植及心胸腺联合移植,在短期环孢素作用下,移植心及胸腺均获长期存活;在移植物长期存活组IL-4保持较高水平,而IL-2处于较低水平。结论:经胸腺注射胸腺细胞可以诱导对同种异体心脏及胸腺的耐受;胸腺移植有利于耐受的诱导和维持。

Objective To explore the role of allo heart and thymus transplantation by intrathymic inoculation of thymocytes. Methods Wistar recipients were given intrathymic injection of allo thymocytes （2 × 10^7） 14 days before the heart and/or thymus transplantation. Graft survival, histopathology, levels and mRNA expressions of IL-2, IL-4 in serum and cardiac-grafts were investigated. Results Heart transplantation and heart-thymus composite transplantation with the treatment of CysA for 7 or 14 days prolonged graft survival. Heart transplantation and heart-thymus composite transplantation with intrathymic thymocytes injection induced the long-term survival of allo-grafts transiently immunosuppressed with CysA; IL-4 maintained at high levels but IL-2 kept at low levels in grafts in long-term survivals. Conclusion Intrathymic inoculation of allo thymoctyes can induce immune tolerance for both cardiac transplantation and heart-thymus combined transplantation in rats. Thymus graft may play a role in the induction and maintenance of central tolerance.