Transplantation. 2011 May 27;91(10):1065-74. doi: 10.1097/TP.0b013e318215e742.
Long-term acceptance of transplanted organs without requirement for indefinite immunosuppression remains the ultimate goal of transplant clinicians and scientists. This clinical state of allograft acceptance termed "operational tolerance" has been elusive in routine practice. However, there are published reports of recipients where immunosuppression has been discontinued, by intention or patient noncompliance, in which the outcome is a nondestructive immune response and normal function. The question now arises how clinical operational tolerance might be achieved in the majority of recipients. This review provides an overview of current approaches to achieve operational tolerance, including the use of donor bone marrow and depletion of recipient T cells and the resistance of liver transplants to rejection. It also describes the key role of clinical immune monitoring and future approaches to tolerance induction including inhibition of T-cell signaling, manipulation of costimulatory pathways, and expansion of regulatory T cells. The principles of these experimental approaches may ultimately be extended to provide safe and effective control of transplant rejection and induction of clinical operational tolerance.
长期接受移植器官而无需无限期使用免疫抑制剂仍然是移植临床医生和科学家的最终目标。这种被称为“免疫耐受”的同种异体移植接受的临床状态在常规实践中难以实现。然而，有报道称，一些接受者因意图或患者不遵医嘱而停止使用免疫抑制剂，其结果是免疫反应无破坏性且器官功能正常。现在的问题是如何在大多数接受者中实现临床免疫耐受。本文综述了目前实现免疫耐受的方法，包括使用供体骨髓和耗竭受体 T 细胞以及肝脏移植对排斥反应的抵抗力。本文还描述了临床免疫监测的关键作用和未来诱导耐受的方法，包括抑制 T 细胞信号传导、调控共刺激途径和扩增调节性 T 细胞。这些实验方法的原则最终可能会扩展到安全有效地控制移植排斥反应和诱导临床免疫耐受。
