The Liver Unit, Queen Elizabeth Hospital Birmingham, Birmingham, United Kingdom.
Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham, United Kingdom.
Front Immunol. 2020 Jun 22;11:1227. doi: 10.3389/fimmu.2020.01227. eCollection 2020.
The liver is an important contributor to the human immune system and it plays a pivotal role in the creation of both immunoreactive and tolerogenic conditions. Liver transplantation provides the best chance of survival for both children and adults with liver failure or cancer. With current demand exceeding the number of transplantable livers from donors following brain death, improved knowledge, technical advances and the desire to prevent avoidable deaths has led to the transplantation of organs from living, ABO incompatible (ABOi), cardiac death donors and machine based organ preservation with acceptable results. The liver graft is the most well-tolerated, from an immunological perspective, of all solid organ transplants. Evidence suggests successful cessation of immunosuppression is possible in ~20-40% of liver transplant recipients without immune mediated graft injury, a state known as "operational tolerance." An immunosuppression free future following liver transplantation is an ambitious but perhaps not unachievable goal. The initial immune response following transplantation is a sterile inflammatory process mediated by the innate system and the mechanisms relate to the preservation-reperfusion process. The severity of this injury is influenced by graft factors and can have significant consequences. There are minimal experimental studies that delineate the differences in the adaptive immune response to the various forms of liver allograft. Apart from ABOi transplants, antibody mediated hyperacute rejection is rare following liver transplant. T-cell mediated rejection is common following liver transplantation and its incidence does not differ between living or deceased donor grafts. Transplantation in the first year of life results in a higher rate of operational tolerance, possibly due to a bias toward Th2 cytokines (IL4, IL10) during this period. This review further describes the current understanding of the immunological response toward liver allografts and highlight the areas of this topic yet to be fully understood.
肝脏是人体免疫系统的重要贡献者，在产生免疫反应和耐受条件方面发挥着关键作用。肝移植为肝功能衰竭或癌症患儿和成人提供了最佳的生存机会。由于目前的需求超过了脑死亡后供体可移植肝脏的数量，因此，提高认识、技术进步以及预防可避免死亡的愿望导致了从活体、ABO 不相容（ABOi）、心脏死亡供体和基于机器的器官保存中移植器官的情况，其结果可以接受。从免疫学角度来看，肝移植物是所有实体器官移植中最耐受的。有证据表明，在没有免疫介导的移植物损伤的情况下，约 20-40%的肝移植受者可以成功停止免疫抑制，这种状态被称为“操作性耐受”。肝移植后无需免疫抑制是一个雄心勃勃但并非无法实现的目标。移植后最初的免疫反应是由固有系统介导的无菌炎症过程，其机制与保存再灌注过程有关。这种损伤的严重程度受移植物因素的影响，并可能产生重大后果。几乎没有实验研究阐明了对各种形式的肝移植同种异体的适应性免疫反应的差异。除了 ABOi 移植外，肝移植后很少发生抗体介导的超急性排斥反应。肝移植后常见 T 细胞介导的排斥反应，其发生率在活体或已故供体移植物之间没有差异。在生命的第一年进行移植会导致更高的操作性耐受率，这可能是由于在此期间偏向 Th2 细胞因子（IL4、IL10）。这篇综述进一步描述了目前对肝同种异体移植物免疫反应的理解，并强调了该主题尚未完全理解的领域。
