混合胸腺移植诱导皮肤移植物免疫耐受的实验研究  

Tolerance to donor skin graft by grafting with mixed fetal F344 rat and BALB/c mouse thymus in nude mice

作　　者：解志杰[1] 吴军[1] 郑峻松[1] 彭双发[1] 

机构地区：[1]第三军医大学西南医院全军烧伤研究所

出　　处：《第三军医大学学报》2004年第23期2117-2119,共3页Journal of Third Military Medical University

基　　金：国家自然科学基金资助项目 ( 30 2 0 0 2 6 1)~~

摘　　要：目的　通过建立混合胸腺移植模型 ,对混合胸腺移植诱导皮肤移植物免疫耐受及其机制进行初步研究。方法　混合胎胸腺移植 3个月后 ,进行异基因皮肤移植 ,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+ CD2 5 + T细胞的百分率 ,利用免疫组化观察宿主骨髓源细胞在胸腺移植物内的分布情况。利用脾细胞过继转移 ,观察对异种供体抗原已产生耐受的受者脾细胞 ,能否将耐受状态过继转移至正常BALB c小鼠。结果　混合胸腺移植 3个月后 ,受体外周血白细胞中CD4+ CD2 5 + T细胞的百分率为 (2 83± 0 2 0 ) % ,与正常BALB c小鼠相比 ,相差不显著。免疫组化染色显示 ,在移植胸腺内宿主源MHC Ⅱ分子阳性细胞主要位于髓质 ,并具有典型树突样外观。将对F3 44大鼠皮肤已产生耐受的脾细胞 ,过继转移至免疫健全的BALB c小鼠 ,可特异延长胸腺供体来源的F3 44大鼠皮肤移植物的平均存活时间。结论　通过胸腺移植诱导的免疫耐受 ,主要是以胸腺内的中枢排除机制以及调节性T细胞的免疫抑制作用为主 ,而且此种耐受具有一定的“可转传性”。Objective To establish the model of mixed thymus transplantation by grafting with fetal F344 rat thymus and BALB/c mouse thymus in nude mice and to explore the mechanisms of tolerance to donor skin graft. Methods Three months after mixed thymic graft transplantation, skin grafting was performed and the reconstitution of CD4+CD25+T cell subsets in the recipients was detected by flow cytometry. The expressions of host MHC class Ⅰ and MHC class Ⅱ in thymic grafts were observed by immunohistochemistry. Viable whole splenocytes from mixed thymus-grafted nude mouse were adoptively transferred into syngeneic normal BALB/c mice. Then full thickness F344 rat skin and third-party C57BL/6 mouse skin samples were grafted simultaneously. Results After mixed thymus transplantation, efficient reconstitution of mouse CD4+CD25+T cells in the peripheral blood was observed. Thymic grafts showed densely repopulating thymocytes that stained with mAbs for mouse MHC class Ⅰ in the deep cortex and medulla compartments. Furthermore, host-derived MHC class Ⅱ positive cells with the appearance of dendritic cells were clearly present and well distributed in the medulla. In adoptive splenocyte transfer experiments, F344 rat skin grafts were significantly prolonged as compared with the third-party allogeneic C57BL/6 mouse skin grafts. Conclusion Tolerance to donor skin grafts can be transferred by splenocytes from tolerant mice to secondary recipients. The major mechanisms involved in the induction of tolerance may be central deletion within the thymic graft and immune regulation of regulatory T cells.

关 键 词：胸腺移植 免疫耐受 皮肤移植 

分 类 号：R392.4[医药卫生—免疫学] R622.1[医药卫生—基础医学]