临床器官移植免疫耐受诱导的发展和突破

The development and breakthrough of clinical organ transplanttolerance induction

器官移植后长期使用免疫抑制剂具有一系列毒副作用，影响患者和移植物的长期存活。对于患者和器官移植医生而言，诱导免疫耐受是最终极的研究目标。然而，目前对此临床尚缺少有效的实验方案、合适的免疫检测手段，对于完全停药面临的一些伦理和安全问题亦缺乏成熟的建议，因此器官移植”可控耐受”在临床上很难实现。尽管面临种种困难，目前仍然有一些中心谨慎构建了以长期存活为目标的诱导器官移植免疫耐受的处理方案，并取得部分成功。本文对目前临床成功诱导器官移植免疫耐受的方案进行简要综述，包括主动逐渐停药诱导移植免疫耐受，通过混合嵌合诱导器官移植免疫耐受以及调节性T细胞在临床免疫耐受中的应用。

The long-term use of immunosuppressive agents after organ transpiantation is associated with many undesirable side effects which may limit the survival of pa- tients and transplanted organs. To patients and transplant surgeons, organ transplantation tolerance is the ultimate goal to improve patientrs quality of life. The clinical state of al- lograft acceptance termed ＂operational tolerance＂ has re- mained infrequent in clinical transplantation because of the lack of validated assays or biomarkers predictive of tolerance and the concerns about the safety and ethics of complete withdrawal of immunosuppression. Despite these barriers, a number of investigators have continued to conduct well-de- signed studies with the long-term goal of inducing clinical transplantation tolerance. This review provides an overview of the currently successful approaches to achieve clinical op- erational tolerance, including using immunosuppression slowwithdrawal in organ transplantation, transplantation toler- ance through mixed chimerism and clinical application of T regulatory cells in tolerance.