CD8^+T细胞依赖的急性移植物抗宿主病小鼠模型的建立  

Establishment of Mouse Model of CD8^+ T Cell-mediated Acute Graft Versus Host Disease

作　　者：丘凌[1,2] 何珊[2] 曹琦[2] 张雁云[2] 黄瑞[1] 

机构地区：[1]苏州大学医学院 [2]上海交通大学医学院上海市免疫学研究所,上海200025

出　　处：《实验动物与比较医学》2006年第4期213-217,共5页Laboratory Animal and Comparative Medicine

摘　　要：目的建立CD8^+T细胞依赖的急性移植物抗宿主病(GVHD)小鼠模型。方法分别以主要组织相容性抗原(MHC)相同,而次要组织相容性抗原(miHAs)不同的8～12周龄C3H．SW(H-2D^b,CD45．2^+)和B6/SJL(H-2D^b,CD45．1^+)雌性小鼠为供受体,从供体骨髓分离去除T细胞的骨髓细胞(T BM),与其脾脏和淋巴结来源的CD8^+T细胞混合,经尾静脉输注给受致死剂量^(137)γ照射的受体鼠。观察移植后受体的体重、毛色、皮肤和生存率的变化,并用流式细胞术(FACS)和组织病理学进一步分析受鼠靶器官细胞浸润和损伤状况。结果移植后受体鼠出现体重明显减轻、毛发脱落、皮肤溃疡等表现,并在28d后出现死亡；FACS证实浸润受鼠骨髓、脾脏和肝脏的细胞主要为CD45．2^+的供鼠细胞,实验组中还有大量CD45．2^+CD8^+T细胞浸润；组织病理学发现肝脏中大量淋巴细胞浸润,皮肤结构破坏,组织坏死。结论成功建立了miHAs不匹配的异基因骨髓移植诱导的CD8^+ T细胞依赖的GVHD动物模型,该模型模拟了目前临床病人采用的同种异基因骨髓移植配型方式,可为异基因骨髓移植GVHD发病机理及该病的防治研究提供良好的实验平台和工具。Objective To establish a mouse model of CD8^＋T cell-mediated acute graft versus host disease（GVHD）. Methods Female C3H.SW（H-2D^b, CD45.2^＋）mice was used as donors and B6/SJL（H- 2D^b, CD45.1^＋）mice as recipients, both of them are MHC-identical but miHA-mismatched. Before transplantation, the B6 recipients received ^137 γ ray （9.5 Gy） TBI administered in three treatments from a ^137Cs source, then the T cell-depleted bone marrow （T-BM） cells and CD8^＋T cells from C3H.SW donors were injected immediately via tail vein. Results Two of the recipients injected with C3H.SW T-BM and C3H.SW CD8^＋T cells died 28 days and one died 70 days after transplantation. The recipients injected only with C3H.SW T-BM were still alive within 70 days after transplantation. B6 mice without transplantation died within 6-10 days after irradiation. Flow cytometric analysis showed that mononuclear cells from the bone marrow, spleens and livers of B6 mice derived from the donor, and part of mononuclear cells from the spleens and livers was CD45.2^＋, CD8^＋T cell. Pathologic examination of the liver showed that the accumulation of mononuclear cells was in the portal areas of the liver. The structure of skin was destroyed. Conclusions The miHA-mismatched mouse model was CD8^＋T cell-mediated acute GVHD model. The MHC-identical, multiple miHA mismatched mouse model is analogous to human clinical miHA mismatched bone marrow transplantation, which can be used as a good tool for study of pathogenesis and prophylaxis of GVHD.

关 键 词：CD8^+T CELL 移植物抗宿主病(GVHD) 动物模型 

分 类 号：R-332[医药卫生]