CD4^+CD25^+调节性T细胞在维持小鼠肝脏移植自发性免疫耐受状态中的作用

Impact of CD4^+CD25^+ Regulatory T Cells in Maintenance of Spontaneous Immunotolerance in Mouse Liver Transplantation

目的探讨CD4+CD25+调节性T细胞在维持小鼠肝脏移植免疫耐受状态中的作用。方法进行小鼠原位肝脏移植,诱导出移植免疫耐受后,向受体注射抗CD25抗体(PC61)以去除CD4+CD25+T细胞,检测受体内CD4+CD25+T细胞数量及叉状头/翅膀状螺旋转录因子(Foxp3)的表达以确定CD4+CD25+T细胞完全被清除,同时观察受体生存时间。结果与同种同系小鼠肝脏移植结果相似,同种异系肝脏移植小鼠的生存时间亦均超过70 d。移植免疫耐受诱导后,PC61不同注射方案均能完全去除受体小鼠肝脏、脾脏及血液中的CD4+CD25+T细胞,且移植肝脏中Foxp3 mRNA的表达也明显降低,表明完全去除了CD4+CD25+调节性T细胞,但肝脏移植动物生存时间并未受到影响。结论 CD4+CD25+调节性T细胞对于小鼠肝脏移植自发性免疫耐受的维持并非必需。

Objective To approach the role of CD4^＋ CD25^＋ regulatory T cells in the maintenance of immuno- tolerance in mouse liver allograft. Methods The mouse orthotopic liver transplantation was performed. After the liver transplantation immunotolerance induction, anti-CD25 monoclonal antibody （PC61） was injected into the recip- ients with a delayed timing to remove the CD4^＋ CD25^＋ T cells. The percentage of CD4^＋ CD25^＋ T cells and the ex pression of fork-head/winged helix transcription factor （Foxp3） in the recipients were examined. Furthermore, the survival time of the recipient was observed. Results C3H/HeJ recipients receiving DBA/2 hepatic allografts sur vived over 70 d as in the syngeneic liver transplantation （C3H/HeJ recipients receiving C3H/HeJ hepatic grafts）. With various protocols of the delayed PC61 treatment, the CD4^＋ CD25^＋ T cell was completely disappeared as ob- served. However, the removal of CD4^＋ CD25^＋ regulatory T cells after the induction of transplantation immunotoler ance did not affect the survival of hepatic allografts. Conclusion CD4^＋ CD25^＋ regulatory T cells are not essential for the maintenance of spontaneous mouse liver transplantation immunotolerance.