目的：选择性去除骨髓移植物中异基因反应性淋巴细胞，特异性抑制移植物抗宿主病（GVHD）。方法：用携带有FasL基因的重组腺病毒转染Balb/c小鼠来源的树突状细胞（dendritic cells, DC)，并与C57BL/6小鼠骨髓细胞移植物共培养，把经过这种处理的骨髓细胞移植物移植给Balb/c受体小鼠（C57BL/6→Balb/c小鼠GVHD 模型 ，H-2b→H-2d），然后观察、比较各组GVHD表现。结果：致死剂量照射的受体鼠在接受经FasL-DC处理的供体骨髓细胞移植后，没有出现明显的GVHD表现，生存期显著延长,3个月时生存率80％以上。但对照组2周后均出现了明显的GVHD症状，腹泻、脱毛和靶组织淋巴细胞浸润等，生存期没有超过30 d。结论：转染FasL基因的DC可有效去除骨髓移植物中异基因反应性T淋巴细胞，移植用这种方法处理过的骨髓，能够有效抑制GVHD的发生。

Objective：To alleviate graft versus host disease(GVHD) via depletion of alloreactive cells from haematopoietic stem cell grafts. Methods：Balb/c mice dendritic cells genetically engineered to express FasL were cultured with C57BL/6 mice stem cell grafts, and the modified stem cell grafts were used in a C57BL/6 to Balb/c mice GVHD model system (H-2b→H-2d). Then the GVHD clinical manifestations(diarrhea, depilate, lymphocytes infiltration in target tissues) were observed and compared.Results：Recipients that received donor haematopoietic stem cell grafts pretreated with FasL-DC did not develop lethal GVHD, and their survival was also surprisingly prolonged. In contrast, recipients receiving untreated allogeneic grafts displayed all clinical signs of acute GVHD, and died within 30 days after transplantation.Conclusion：DC transfected with FasL gene can prevent GVHD by selective removal of alloreactive cells from haematopoietic stem cell grafts.

R730.5 R979.1

全军医学科研十五计划面上项目（01MA159）