胸腺注射供体脾细胞诱导移植心脏免疫耐受的实验研究

目的探讨诱导心脏移植免疫耐受的方法及其产生的可能机制. 方法采用大鼠腹部心脏移植模型,随机分成未处理(Ⅰ)组,胸腺注射供体脾细胞(Ⅱ)组,腹腔注射兔抗鼠淋巴细胞血清(Ⅲ)组,胸腺注射供体脾细胞联合应用兔抗鼠淋巴细胞血清(Ⅳ)组,每组6只大鼠.Ⅱ、Ⅳ组在移植前2 1 d将供体脾细胞2.5×107个注射到受体胸腺,Ⅲ、Ⅳ组受体腹腔注射兔抗鼠淋巴细胞血清(ALS)1 ml,然后行异位心脏移植.观察移植心脏存活时间,供心病理学改变及供、受体间的混合淋巴细胞反应(MLR). 结果Ⅳ组供心平均存活时间(MST)为(81.8±7.6)d,较Ⅰ组(7.3±1.0)d、Ⅱ组( 7.8±1.0)d、Ⅲ组(8.2±1.2)d显著延长,差异有显著性意义(P＜ 0.01 );供心仅见少量炎性细胞浸润;供、受体间MLR较正常对照组显著降低,差异有显著性意义(P＜0.01). 结论胸腺注射供体脾细胞联合应用ALS能成功诱导心脏移植的免疫耐受;胸腺内特异性T细胞克隆消除可能与免疫耐受的形成有关.

Induced tolerance to cardiac allografts with intrathymic injection of donor spleen cells

OBJECTIVE: To study the methods and mechanisms of immune tolerance in cardiac transplantation. METHODS: Male DA rat hearts were transplanted to male Lewis rats using Ono's model and randomly divided into four groups: untreated (group I), intrathymic injection of 2.5 x 10(7) DA splenocytes to Lewis rat (group II), intraperitoneal injection of 1 ml rabbit anti-rat lymphocyte serum (ALS) to Lewis recipient (group III), intrathymic injection of 2.5 x 10(7) DA splenocytes combined with intraperitoneal injection of 1 ml rabbit anti-rat lymphocyte serum (ALS) to Lewis recipient (group IV). 21 days later heart transplantation was performed. Mean survival time (MST), histological changes and mixed lymphocyte reaction (MLR) were measured after operation. RESULTS: In the group of intrathymic injection of spleen cells combined with ALS treatment, the survival time of heart allografts MST: (81.8 +/- 7.6)d] was significantly longer than in the groups I MST: (7.3 +/- 1.0) d], group II MST:(7.8+/- 1.0)d], and group III MST(8.2 +/- 1.2) d, P < 0.01]. Only a few inflammatory cells infiltrated in cardiac allografts in group IV. MLR of group IV were significantly decreased compared with those of the normal control (P < 0.01). CONCLUSIONS: The role of thymus as a special site for induction and maintenance of specific immunological unresponsiveness to organ allografts was confirmed. T cell clonal deletion may play an important role in this immune tolerance.