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目的通过猪-猴心脏移植模型来探讨异种胸腺修饰对移植物存活时间的影响,并在此基础上,研究异种器官移植中T细胞的作用及诱导异种T细胞中枢性耐受的可能性。方法将受体(中国猕猴)分为4组:(1)空白组:对受体不作任何处理。(2)照射组:于心脏移植前30 d(d30),接受60Co 3Gy全身剂量,余同空白组。(3)胸腺注射组:于心脏移植前21 d(d21),胸腺内注射供体脾细胞(5×107),余同空白组。(4)照射+胸腺注射组(8只):于心脏移植前28 d(d28),即1.5月龄时接受60Co 3Gy全身剂量,心脏移植前21 d(d21),胸腺内注射供体脾细胞(5×107),余同空白组。结果照射+胸注组存活期较空白组明显延长(P<0.01),照射+胸注组存活期较胸注组和照射组延长(P<0.05)。CD4+、CD8+与同期未照射的另两组相比有显著性差别(P<0.01),但照射的两组同期相比差别不大(P>0.05)。照射+胸腺注射组于手术当天MLR刺激效应较空白组、照射组下降明显(P<0.01),同时单独胸腺注射组与照射组、照射+胸腺注射组相比,刺激效应也有所下降(P<0.05)。结论(1)异种胸腺修饰对CD4+、CD8+T细胞亚群的生成与分布情况并无影响,但其针对异种抗原反应能力有所下降。(2)异种胸腺注射可支持T细胞的重建和诱导供体特异性的T细胞功能抑制或耐受,并有效地延长供心存活时间。
OBJECTIVE: To investigate the effects of xenogeneic thymic modification on graft survival time by pig-monkey heart transplantation model and to study the role of T cells in xenotransplantation and the possibility of inducing central tolerance of xenogeneic T cells. Methods The recipients (Chinese macaques) were divided into 4 groups: (1) blank group: no treatment on the recipient. (2) irradiation group: 30 d before cardiac transplantation (d30), receiving 60Co 3Gy systemic dose, the rest of the blank group. (3) Thymus injection group: 21 days before heart transplantation (d21), donor spleen cells (5 × 107) were injected into the thymus, remaining in the blank group. (4) Irradiation + thymus injection group (8): The whole body dose of 60Co 3Gy was administered 28 days before heart transplantation (d28), 1.5 months of age, 21 days before heart transplantation (d21) (5 × 107), the same blank group. Results The survival time of irradiation + chest injection group was significantly longer than that of blank control group (P <0.01). The survival time of irradiation + chest injection group was longer than that of injection and injection group (P <0.05). CD4 + and CD8 + were significantly different from those of the other two groups (P <0.01). However, there was no significant difference between the two groups in the same period (P> 0.05). Compared with the blank group, the irradiation effect in the irradiation + thymus injection group was significantly decreased on the day of surgery (P <0.01), and the stimulation effect was also decreased in the thymus injection group compared with the irradiation group and the thymus injection group (P < 0.05). Conclusion (1) Xenogeneic thymus has no effect on the formation and distribution of CD4 + and CD8 + T cell subsets, but its ability to respond to different antigens is decreased. (2) Xenogeneic thymus injection can support the reconstruction of T cells and induce donor-specific T cell function inhibition or tolerance, and effectively prolong the time of cardiac survival.