耐受T细胞抑制NK细胞和巨噬细胞对大鼠皮肤移植物的排斥  

Suppression of NK cells by immune tolerant T cells and macrophage activity against rat skin graft

作　　者：解志杰[1] 吴军[1] 郑峻松[1] 彭双发[1] 易绍萱[1] 陈希炜[1] 贺伟峰[1] 

机构地区：[1]第三军医大学附属西南医院全军烧伤研究所,重庆市器官移植基础研究所,创伤烧伤复合伤国家重点实验室,重庆400038

出　　处：《第三军医大学学报》2003年第21期1892-1895,共4页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目(30200261);国家自然科学基金资助重大项目(39993430-2)~~

摘　　要：目的 了解NK细胞和巨噬细胞在T细胞缺乏或T细胞成功重建的情况下对异种移植物排斥的作用。方法在无胸腺裸小鼠、通过混合胸腺移植重建T细胞后裸小鼠和正常免疫健全小鼠分别进行F344大鼠皮肤移植,观察异种皮肤移植物的存活情况,并利用流式细胞仪检测各组受体动物外周血中CD4+和CD8+T细胞的百分率,利用ConA增殖实验和混合淋巴细胞培养检测其体外功能状态。结果 在没有清除受体体内NK细胞和巨噬细胞的情况下,正常无胸腺BALB/c裸小鼠上移植的F344大鼠皮肤移植物发生了排斥,平均存活时间为(20.50±2.38)d;而在裸小鼠左肾包膜下移植的F344胎大鼠胸腺组织,却能够正常发育,并有效重建了受体的T细胞免疫,而且诱导了F344大鼠皮肤移植物的长期存活。结论NK细胞和巨噬细胞在异种移植物的排斥中起十分重要的作用,不同组织对NK细胞和巨噬细胞细胞毒性的易感性可能存在一定的差异。对异种供体抗原已产生耐受的T细胞可抑制受体体内NK细胞和巨噬细胞对异种移植物的排斥。Objective To evaluate the roles of natural killer (NK) cells and macrophages in the rejection of discordant xenografts in nude mice and T cell-reconstitution nude mice. Methods F344 rat skins were respectively transplanted into athymic nude mice, T cell-reconstitution nude mice grafted with mixed fetal thymus and normal eu-thymic mice in the absence of NK cells and macrophages. The survival rate of the grafted xenografts was observed by light microscopy. Percentages of T cell subsets in the peripheral blood in recipient animals were determined by flow cytometry. Mixed lymphocyte reaction assay and induction of splenocytes by ConA were performed after rejection of the skin graft. Results In the absence of NK cells and macrophages depletion, mean survival time (MST) in normal euthymic mice was (6.75±0.50) days. There was modest prolongation in athymic nude mice [MST=(20.50± 2.38) days]. After T cell-reconstitution in nude mice, the survival of F344 rat skin grafts was significantly prolonged as compared with that in athymic nude mice [mean survival time (78.00±34.89) days vs (20.50±2.38) days, P <0.001]. However, athymic nude mice accepted F344 rat thymus tissues indefinitely despite without depletion of NK cells and macrophages in the recipients. Conclusion NK cells and macrophages play an important role in the rejection of discordant xenografts. Different tissues may result in different degrees of susceptibility to NK cell and macrophage cytotoxicity. Moreover, NK cell- and macrophage-mediated rejection of xenogeneic skin grafts may be inhibited by tolerant T cells in the recipient.

关 键 词：NK细胞 巨噬细胞 胸腺移植 异种移植 

分 类 号：R392.12[医药卫生—免疫学] R392.4[医药卫生—基础医学]