猪到猴异种胸腺修饰对受体心脏移植物存活时间及外周血T细胞的影响  

Study on the Effect of the Survival Time and the T cells in the Discordant Heart Xenotransplantation Produced by Intrathymic Inoculation with Xenogeneic Antigen Using the Model of Pig to Monkey

作　　者：瞿冀琛[1] 沈振亚[2] 姜格宁[1] 丁嘉安[1] 倪斌[2] 张治[2] 何建明[2] 余云生[2] 叶文学[2] 

机构地区：[1]上海市肺科医院胸外科,上海200433 [2]苏州大学附属第一医院心胸外科和器官移植研究室,江苏苏州215006

出　　处：《苏州大学学报（医学版）》2005年第5期768-771,795,共5页Suzhou University Journal of Medical Science

基　　金：国家自然科学基金资助项目(编号:39770731)

摘　　要：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 This study was designed to investigate the effect of survival time and T cells on the delayed xenograft rejection caused by intrathymic injection of xenogeneic antigen in the discordant cardiac xenotransplantation, and to investigate the possibility of inducing the tolerance for cardiac xenografts. Methods In this experiment, pig and monkey were, respectively, selected as donor and recipient. Donor and recipient were divided randomly into four groups. In the blank group （group A） recipients didn＇t accept any treatments but heart xenotransplantation; In the whole body irradiation （WBI） group （group B） 3 Gy（^60Co） was received on d30 before transplantation, In the intrathymic injection group（group C） monkeys were pretreated by the intrathymic injection of pig spleen cells （5 × 107） on d21 before transplantation, the other treatments were the same as that in group A. In the irradiation and intrathymic injection group （group D） monkeys were pretreated by WBI and the intrathymic injection of pig spleen ceils at the time just as that in group B and group C. In every group, monkeys were performed heterotopic heart xenotransplantation in abdomen in order to observe the survival time of cardiac xenografts. Results （1） Survival time of donor heart in group D（91.1 ± 22.8h） was significantly longer than group B（42.56 ± 1.4h） and group A（35.6 ± 2.2h） （ P 〈 0.01）, there was also evident difference between group D and group C（P 〈 0.05）. （2） The result of CD4. CD8 testing in peripheral blood have no difference between groupB and groupD before transplantation（P 〉 0.05）. （3）The results of MLR showed that there is significant reduction in group D than in group A and B （P 〈0.01） when the recipient splenocyte responded to donor stimulator. There was different stimulating effect between in group C and D （P 〈 0.05）. Conclusions （1） In this model, Intrathymic inoculation can＇t influence the percent of CD4 ^＋ and CD8 ＋ T cells in p

关 键 词：胸腺修饰 异种心脏移植 免疫耐受 混合淋巴细胞培养 

分 类 号：R392.4[医药卫生—免疫学]