同系或同种胸腺与异种胸腺混合移植诱导T细胞免疫耐受的实验研究  

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：《中国现代医学杂志》2005年第17期2607-2611,2614,共6页China Journal of Modern Medicine

基　　金：国家自然科学青年基金项目(No:30200261)

摘　　要：目的探讨同系或同种胸腺与异种胸腺混合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裸小鼠外周血中CD3+CD4+T细胞,用单向混合淋巴细胞培养了解受者T细胞对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。用ELISA法检测受体血清中抗DNA自身抗体。结果胎胸腺移植4个月后,受者裸小鼠中CD3+CD4+T细胞重建良好;T细胞对ConA以及无关的SD鼠异种淋巴细胞的反应性强,而对移植胸腺供体来源的淋巴细胞不发生增殖反应;受者对移植胸腺供体来源鼠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。异种胸腺移植组发生消耗性疾病死亡高,抗DNA自身抗体明显高于混合胸腺移植组。结论同系或同种异种胎胸腺混合移植可诱导受者T细胞对供者移植物的免疫耐受。[Objective] To explore feasibility of inducing T cells immune tolerance by transplanting with mixed fetal syngeneie or allogeneie and xenogeneie thymus. [Method] The xenogeneie thymus grafting, mixed syngeneie and xenogeneie thymus grafting , mixed allogeneie and xenogeneie thymus grafting model in nude mice was established. Four months after thymus transplantation under the double kidney capsule in BALB/e nude mice, the reeonstitution of CD3^＋CD4^＋T lymphocyte in the recipients was detected by flow eytometry and ConA, lymphocyte from F344 rat or C57BL/6 mouse or SD rat or BALB/e mouse stimulation T cell reaction was measured by mixed lymphocyte reaction （MLR）, skin grafting was performed and grafts survive time was evaluated. Incidence of autoimmune disease was compared. Anti-DNA autoantibodies of recipient＇ s sera were tested by ELISE. [Results] After thymus transplantation, efficient reeonstitution 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. Level of anti-DNA autoantibodies in the sera of xenogeneie group recipients were significantly higher than that of mixed group. [Conculsion] Grafting mixed syngeneie or allogeneie and xenogeneie thymus into nude mice can efficiently reconstitute the CD4. This method can induce donor-specific transplantation tolerance.

关 键 词：胸腺移植 免疫耐受 自身免疫 皮肤移植 

分 类 号：R617[医药卫生—外科学]