Division of Transplantation Immunology and Mucosal Biology, Institute of Liver Studies, Medical Research Council Centre for Transplantation, Faculty of Life Sciences and Medicine, King's College London, London, UK.
CRF GMP Unit, NIHR Biomedical Research Centre at Guy's and St Thomas' NHS Foundation Trust and King's College London, London, UK.
Transpl Int. 2017 Aug;30(8):776-784. doi: 10.1111/tri.12998.
Modern immunosuppression drug regimens have produced excellent short-term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants, and therefore, liver transplantation offers an attractive setting in which to study tolerizing therapies. CD4 CD25 FOXP3 regulatory T cells (Tregs) are crucial for maintenance of self-tolerance and prevention of autoimmune disease and are therefore an appealing potential candidate for use as a tolerizing cell therapy. In this review, we summarize the evidence from drug withdrawal trials of spontaneous operational tolerance in liver transplantation, the unique immunology of the hepatic microenvironment, the evidence for the use of CD4 CD25 FOXP3 regulatory T cells as a tolerance inducing therapy in liver transplantation and the challenges in producing clinical grade Treg cell products.
现代免疫抑制药物方案在肝移植后产生了极好的短期存活率，但人们普遍认为，这些药物的副作用仍然是导致长期效果不尽如人意的一个重要因素。肝脏具有独特的耐受特性，这体现在与其他实体器官移植相比，肝移植受者的手术耐受率更高，因此，肝移植为研究耐受治疗提供了一个有吸引力的环境。CD4 CD25 FOXP3 调节性 T 细胞（Tregs）对于维持自身耐受和预防自身免疫性疾病至关重要，因此是作为耐受细胞治疗的潜在候选者。在这篇综述中，我们总结了肝移植中自发手术耐受的药物停药试验、肝脏微环境的独特免疫学、CD4 CD25 FOXP3 调节性 T 细胞在肝移植中作为诱导耐受治疗的证据，以及生产临床级 Treg 细胞产品所面临的挑战。
