同基因造血干细胞移植免疫重建诱导小鼠皮肤移植耐受

Induction of transplantation tolerance to fully mismatched skin allografts in mice by syngeneic hematopoietic stem cells

背景:器官移植耐受的最佳效果是能够诱导对移植抗原的特异性免疫耐受。目的:探讨小鼠异基因皮肤移植后,通过受体同基因造血干细胞移植重建免疫系统诱导移植皮肤免疫耐受的可行性。方法:取BALB/c小鼠骨髓。以C57BL/6小鼠为供体,BALB/c小鼠为受体,进行异基因皮肤移植;32只受体鼠随机均分为4组:移植对照组、环孢素A组、照射组和骨髓移植组。结果与结论:照射组小鼠10d内全部死亡,外周血白细胞数呈持续性降低;而骨髓移植组小鼠长期存活,白细胞数全身照射后6d降到最低,之后持续性增高,照射后21d与环孢素A组比较差异无显著性意义(P>0.05),移植皮肤存活时间显著长于其他各组(P<0.01),其淋巴细胞浸润及组织结构破坏明显减少,小鼠脾细胞对供体小鼠脾细胞增殖反应显著降低。说明同基因骨髓细胞移植重建免疫系统可显著延长小鼠移植皮肤存活时间,可诱导供者特异性免疫耐受。

BACKGROUND：The optimal effect of organ transplantation tolerance is to induce the specific immunologic tolerance to transplantation antigens.OBJECTIVE：To study the possibility of using syngeneic hematopoietic stem cells to reconstitute immune system and induce transplantation tolerance to fully mismatched skin allografts in mice.METHODS：BALB/c mouse marrow was taken.Syngeneic skin transplantation was performed taking C57BL/6 mice as donors and BALB/c mice as recipients.Thirty-two BALB/c mice were randomly divided into four groups：control,cyclosporin A,cyclosporin A ＋ total body irradiation,cyclosporin A ＋ total body irradiation,cyclosporin A ＋ total body irradiation ＋ bone marrow transplantation.RESULTS AND CONCLUSION：In the cyclosporin A ＋ total body irradiation group,all mice died within 10 days and the counts of peripheral blood white blood cells were persistently declined.In the cyclosporin A ＋ total body irradiation ＋ bone marrow transplantation group,mice survived during the experimentation,the counts of peripheral blood white blood cells decreased to the bottom after 6 days of irradiation and then rebounded,and increased to the level of the cyclosporine A group after 21 days of irradiation（P 0.05）.The average survival time of skin grafts in the cyclosporin A ＋ total body irradiation ＋ bone marrow transplantation group was significantly longer than that in the other groups（P 0.01）.There were less infiltrated cells and less destructed tissue,and decreased proliferation of recipient mouse spleen cells in the cyclosporin A ＋ total body irradiation ＋ bone marrow transplantation group than in the other groups.These findings suggest that immune reconstitution with syngeneic bone marrow cells can obviously prolong the survival time of mouse skin allografts and induce donor-specific tolerance.