Benseler Volker, McCaughan Geoffrey W, Schlitt Hans J, Bishop G Alex, Bowen David G, Bertolino Patrick
Centenary Institute and AW Morrow Gastroenterology and Liver Centre, Sydney, NSW, Australia.
Semin Liver Dis. 2007 May;27(2):194-213. doi: 10.1055/s-2007-979471.
Liver transplants are not often rejected in patients weaned from immunosuppression and are spontaneously accepted in some animal models. We review past and recent findings of liver transplantation and propose a unified model in which several mechanisms act in concert to induce and maintain tolerance in both naïve and effector T cell compartments. First, passenger leukocytes migrate to lymphoid tissues and induce apoptosis of alloreactive naïve T cells. Second, antigen-specific activation and subsequent deletion of naïve and effector cells within the liver itself purge the repertoire of alloreactive T cells. Other mechanisms such as microchimerism and migration of donor dendritic cells to the thymus may play a predominant role in maintaining tolerance, and soluble major histocompatibility complex molecules, donor peptides, and regulatory T cells may participate in the induction and maintenance phases. Thus, the major challenge in liver transplantation will be to favor these tolerogenic processes while developing strategies that specifically inhibit alloreactive memory T cells.
在停用免疫抑制药物的患者中，肝移植通常不会被排斥，并且在一些动物模型中能自发被接受。我们回顾了肝移植过去和近期的研究发现，并提出了一个统一模型，其中多种机制协同作用，在初始和效应T细胞区室中诱导并维持免疫耐受。首先，过客白细胞迁移至淋巴组织并诱导同种异体反应性初始T细胞凋亡。其次，肝脏自身内抗原特异性激活以及随后初始和效应细胞的清除，清除了同种异体反应性T细胞库。其他机制，如微嵌合体以及供体树突状细胞迁移至胸腺，可能在维持耐受中起主要作用，可溶性主要组织相容性复合体分子、供体肽和调节性T细胞可能参与诱导和维持阶段。因此，肝移植的主要挑战将是促进这些致耐受过程，同时制定特异性抑制同种异体反应性记忆T细胞的策略。
