Humoral immunity induced at liver xenotransplantation by intravenous infusion of donor′s apoptotic cells
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摘要: 目的 以贵州香猪为供者、中国猕猴为受体的异种肝移植模型,采用静脉输注异种异基因骨髓及凋亡细胞的方法预处理受体,研究凋亡细胞对异种肝脏移植免疫排斥反应的影响,探讨异种肝脏移植免疫耐受的机制.方法 受者猕猴随机分为A、B、C组, A组为阴性对照组, n=6;B组为实验对照组, n=28, 在接受RIC之后,再接受供者贵州香猪的异种异基因骨髓(BM)静脉输注;C组为实验组, n=36, 在接受RIC之后,再接受供者贵州香猪的BM和凋亡细胞同时静脉输注.观察各组受体的生存期,检测受体术后外周血中ALT、TB含量、Foxp3+CD4+CD25+调节性T细胞和T细胞亚群上GITR的表达,检测受体术后第14天移植肝的病理变化和术后第14天受体脾脏CTL杀伤活性.结果 C组肝移植术后经历短暂排斥反应,最终可获免疫耐受并长期存活,其外周血中Foxp3+CD4+CD25+调节性T细胞表达比例在术后第14天渐恢复正常,受体外周血中CD3+CD4+T细胞上GITR表达降低, CD3+CD8+T细胞上GITR表达增加,提高CTL的杀伤活性;B组受体在术后第17~21天死亡,与A、C组相比,外周血血清中ALT、TB含量明显升高,而Foxp3+CD4+CD25+调节性T细胞比例明显降低.结论 供者凋亡细胞静脉输注在异种肝移植中所产生体液免疫耐受的机理,可能是通过诱导受体外周血中CD3+CD4+T细胞上GITR表达降低, CD3+CD8+T细胞上GITR表达增加,提高CTL的杀伤活性来实现的.
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