供体凋亡淋巴细胞诱导移植耐受的免疫学机制初探

发布时间：2018-02-09 00:38

本文关键词： 供体脾淋巴细胞凋亡受体肝脏肝脏抗原递呈细胞吞噬作用细胞因子　出处：《第一军医大学》2006年博士论文　论文类型：学位论文

【摘要】：免疫耐受是解决移植排斥反应的根本方法之一。目前采用的耐受诱导方法多以中央和外周耐受理论为基础形成，但由于各种原因尚未取得预想的结果。凋亡是生物体内的基本生理现象之一，对于维持机体内在平衡非常关键。研究已发现，，凋亡是机体维持免疫系统稳定的重要作用机制，而且凋亡细胞对炎性反应的抑制性调节作用是一种主动的过程：凋亡细胞通过分泌趋化因子、变换细胞膜表面特征“eat-me”分子，诱导吞噬细胞对其进行清除，同时在清除过程中通过巨噬细胞等分泌炎症抑制性因子，如TGFβ、IL-10、PGE_2等造成一个特殊的免疫微环境。正常生理状态下，此过程可以促使相关淋巴细胞对其特征性抗原识别激活后产生免疫耐受，而不是引起炎性免疫应答。根据凋亡细胞能够主动引起免疫耐受这一现象，孙尔维等首次提出利用供体凋亡细胞输注受体诱导供体特异性免疫耐受的理论设想。由此，本课题组前期研究开展了供体凋亡脾淋巴细胞对大鼠心脏、肝脏移植模型诱导耐受的实验研究，发现一定数量的供体凋亡脾淋巴细胞预输注可以诱导大鼠心、肝脏移植模型产生特异性免疫耐受，延长移植存活时间。该发现初步验证了孙尔维等的理论设想，但对于供体凋亡细胞输注如何诱导机体产生非特异性免疫耐受，其内在作用的关键环节和机制是什么，都尚未可知。同时，类似的相关机制研究，国内外都未有报道可以用来参照和解释，而了解供体凋亡细胞诱导移植耐受的内在机制对于深入掌握该理论的中心环节、进一步完善该理论设想，进而指导更有效地实现耐受诱导有
[Abstract]:Immune tolerance is one of the fundamental methods to solve the allograft rejection. Most of the current tolerance induction methods are based on the central and peripheral tolerance theory. However, due to various reasons, the expected results have not been obtained. Apoptosis is one of the basic physiological phenomena in organisms, which is very important to maintain the balance in the body. It has been found that apoptosis is an important mechanism for maintaining the stability of the immune system. Moreover, the inhibitory effect of apoptotic cells on inflammatory response is an active process: apoptotic cells induce phagocytes to clear them by secreting chemokines, transforming "eat-me" molecules on the surface of cell membranes, and inducing phagocytes to clear them. At the same time, during the process of clearance, inflammatory inhibitory factors such as TGF 尾 -IL-10 and PGE-2 were secreted by macrophages, which resulted in a special immune microenvironment. This process can induce the associated lymphocytes to develop immune tolerance after activation of their characteristic antigen recognition rather than inflammatory immune response, according to the phenomenon that apoptotic cells can actively induce immune tolerance. Sun Erwei et al proposed for the first time a theoretical idea of donor-specific immune tolerance induced by donor apoptotic cell infusion. Experimental study on tolerance induced by liver transplantation model showed that a certain number of donor apoptotic splenic lymphocytes preinfused could induce rat heart and liver transplantation model could produce specific immune tolerance. The findings preliminarily verify Sun Erwei's theory, but what is the key link and mechanism of the intrinsic role of donor apoptotic cell infusion in inducing nonspecific immune tolerance. At the same time, there is no domestic and foreign report on similar mechanisms that can be used for reference and explanation, and understanding the intrinsic mechanism of donor apoptosis induced transplantation tolerance is central to a deeper understanding of this theory. Further improve the theoretical assumption, and then guide the more effective implementation of tolerance induction.
【学位授予单位】：第一军医大学
【学位级别】：博士
【学位授予年份】：2006
【分类号】：R392.4

【引证文献】