Institute of Medical Immunology, Charité University Medicine, Augustenburger Platz 1, Berlin, Germany.
Curr Opin Organ Transplant. 2012 Feb;17(1):34-41. doi: 10.1097/MOT.0b013e32834ee69f.
Transfer of human regulatory T cells (Tregs) has become an attractive therapeutic alternative to improve the long-term outcome in transplantation and thus reduce the side-effects of conventional immunosuppressive drugs. Here, we summarize the recent findings on human Treg subsets, their phenotype and in-vivo function.
In the last 2 years, it has become apparent that several Treg subsets exist that specifically regulate Th1-driven, Th2-driven, or Th17-driven immune responses; these subsets are very unstable and rapidly change their phenotype, for example, there is loss of Foxp3 expression upon extensive ex-vivo expansion and only the administration of rapamycin has been shown to be able to interfere reproducibly. New humanized mouse models incorporating human solid-organ grafts have been developed, which have been used to test the human Treg in-vivo function, and the first human Treg-cell products have been tested for safety and efficacy in stem cell transplantation.
With the recent findings, we have gained a better understanding of Treg heterogeneity, plasticity and function. Using the outcomes of clinical trials in stem cell transplantation, we have learned that adoptive therapy of Tregs is well tolerated and we are now awaiting the first result in solid-organ transplantation from the 'ONE Study'.
将人调节性 T 细胞（Tregs）转移作为一种有吸引力的治疗选择，以改善移植的长期结果，从而减少传统免疫抑制药物的副作用。在这里，我们总结了关于人 Treg 亚群及其表型和体内功能的最新发现。
在过去的 2 年中，显然存在几种 Treg 亚群，它们可以特异性地调节 Th1 驱动、Th2 驱动或 Th17 驱动的免疫反应；这些亚群非常不稳定，其表型会迅速变化，例如，在广泛的体外扩增后会失去 Foxp3 的表达，只有雷帕霉素的给药已被证明能够重复地干扰其功能。已经开发出了包含人实体器官移植物的新型人源化小鼠模型，用于测试人 Treg 的体内功能，并且已经测试了第一批人 Treg 细胞产品在干细胞移植中的安全性和疗效。
随着最近的发现，我们对 Treg 的异质性、可塑性和功能有了更好的理解。利用干细胞移植临床试验的结果，我们了解到 Treg 的过继治疗是耐受良好的，我们现在正在等待“ONE 研究”在实体器官移植中的第一个结果。
