Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs.
Immunologic basis of graft rejection and tolerance following transplantation of liver or other solid organs.
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DOI：
10.1053/j.gastro.2010.10.059
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发表时间：
2011-01
期刊：
影响因子：
29.4
通讯作者：
Strom TB
中科院分区：
文献类型：
--
作者：
Sánchez-Fueyo A;Strom TB
器官在同一物种的不同遗传个体之间移植会引起T细胞介导的免疫反应，如果不加以控制，会导致排斥反应和移植物破坏。同种异体免疫反应的效力取决于供者和受者之间通常存在的抗原性差异，以及移植后早期移植物内促炎症细胞因子的表达。在动物模型中的研究已经确定了许多分子，当靶向时，抑制T细胞的激活。此外，这些研究中的一些研究表明，某些免疫干预可以诱导移植耐受，在这种状态下，同种异体移植物被特定地接受，而不需要慢性免疫抑制。耐受性是肝移植的一个重要方面，因为肝脏有一个独特的微环境，促进耐受性而不是免疫力。与在动物模型中诱导耐受方面取得的进展相反，接受器官移植的患者仍然需要非特异性免疫抑制药物。钙调神经磷酸酶抑制剂的发展降低了急性排斥反应的发生率，提高了移植物的短期存活率，但不是长期存活率。然而，长期使用免疫抑制药物会导致肾毒性和代谢紊乱，以及机会性感染和癌症等过度免疫抑制的表现。因此，临床上对药物免疫抑制的研究现状并不理想。我们回顾了最近开发的促进对移植肝脏和其他器官的耐受性的治疗策略，以及可能用于识别最有可能接受或拒绝同种异体移植的患者的诊断工具。
Transplantation of organs between genetically different individuals of the same species causes a T cell–mediated immune response that, if left unchecked, results in rejection and graft destruction. The potency of the alloimmune response is determined by the antigenic disparity that usually exists between donors and recipients and by intragraft expression of proinflammatory cytokines in the early period after transplantation. Studies in animal models have identified many molecules that, when targeted, inhibit T-cell activation. In addition, some of these studies have shown that certain immunologic interventions induce transplantation tolerance, a state in which the allograft is specifically accepted without the need for chronic immunosuppression. Tolerance is an important aspect of liver transplantation, because livers have a unique microenvironment that promotes tolerance rather than immunity. In contrast to the progress achieved in inducing tolerance in animal models, patients who receive transplanted organs still require nonspecific immunosuppressant drugs. The development of calcineurin inhibitors has reduced the acute rejection rate and improved short-term, but not long-term, graft survival. However, long-term use of immunosuppressive drugs leads to nephrotoxicity and metabolic disorders, as well as manifestations of overimmunosuppression such as opportunistic infections and cancers. The status of pharmacologic immunosuppression in the clinic is therefore not ideal. We review recently developed therapeutic strategies to promote tolerance to transplanted livers and other organs and diagnostic tools that might be used to identify patients most likely to accept or reject allografts.
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影响因子：
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