混合胸腺移植诱导免疫耐受和防止发生自身免疫性疾病的实验研究  

Induction of T cell tolerance by transplanting with mixed fetal syngeneic or allogeneic and xenogeneic thymus

作　　者：王锡华[1] 吴军[1] 解志杰[1] 袁军[1] 贺伟峰[1] 陈希炜[1] 易绍萱[1] 

机构地区：[1]第三军医大学西南医院烧伤研究所创伤烧伤复合伤国家重点实验室,重庆400038

出　　处：《医学研究生学报》2005年第6期499-502,共4页Journal of Medical Postgraduates

基　　金：国家自然科学青年基金资助项目(批准号:30200261)

摘　　要：目的:探讨混合胸腺移植诱导移植免疫耐受而不发生自身免疫性疾病的可行性。方法:BALB/c裸小鼠的肾包膜下植入胸腺,建立异种、同系与异种混合、同种与异种混合胸腺移植模型。4个月后,用流式细胞仪技术检测受者外周血中T细胞,用混合淋巴细胞培养了解T细胞对刀豆素A(ConA)以及同种异种淋巴细胞的反应性,异基因皮肤移植观察皮肤移植物存活期。术后6个月内比较各组发生自身免疫性疾病情况,观察胃的组织学变化,用ELISA法检测受者血清中抗DNA自身抗体。结果:胸腺移植后,受者T细胞重建良好;T细胞对ConA及无关的SD鼠淋巴细胞的反应强,而对移植胸腺供者来源的淋巴细胞无增殖反应;受者对胸腺供者来源皮肤移植物不发生排斥,而对无关的SD鼠皮肤移植物发生排斥。异种组发生自身免疫性疾病率高,异种组胃组织有明显的炎性损害,血清中自身抗体明显高,而混合组未观察到明显的炎性改变。结论:同系或同种、异种胎胸腺混合移植,可诱导供者特异性免疫耐受和防止器官特异性自身体免疫性疾病。Objective:To explore feasibility of inducing immune tolerance and prevention of organ specific autoimmune disease by transplanting with mixed fetal syngeneic or allogeneic and xenogeneic thymus. Methods: The xenogeneic thymus grafting, mixed syngeneic and xenogeneic thymus grafting ,mixed allogeneic and xenogeneic thymus grafting model in nude mice was established. Four months after thymus transplantation, the reconstitution of CD3^+CD4^+T cells lymphocyte in the recipients was detected by flow cytometry and ConA, lymphocyte from F344 rat, C57BL/6 mouse, SD rat or BALB/c mouse stimulation T cell reaction was measured by MLR, skin grafts survive time was evaluated. Anti-DNA autoantibodies of recipient's sera were tested by ELISE, and histological changes of recipient's organs and tissues were observed simultaneously. Results: After thymus transplantation, efficient reconstitution of CD3^(+)CD4^(+)T cells in peripheral blood was observed. In MLR, T cell from recipients showed a strong response to either the stimulation of ConA mitogens or SD rat lymphocyte, and were tolerant for thymus donor lymphocyte. Thymus donor skin grafts were significantly prolonged as compared with the third-party SD rat skin grafts. Noted inflammatory lesions in the stomachs in xenogeneic thymus transplantation group but not mixed group were observed. Level of anti-DNA autoantibodies in the sera of xenogeneic!group recipients were significantly higher than that of mixed group. Conculsion: Grafting mixed syngeneic or allogeneic and xenogeneic thymus into nude mice can efficiently induce donor-specific transplantation tolerance and prevent the autoimmune lesions.

关 键 词：胸腺移植 免疫耐受 自身免疫 皮肤移植 

分 类 号：R655.7[医药卫生—外科学]