Feng Gang, Chan Thomas, Wood Kathryn J, Bushell Andrew
Nuffield Department of Surgery, University of Oxford, John Radcliffe Hospital, Oxford, UK.
Curr Opin Organ Transplant. 2009 Aug;14(4):432-8. doi: 10.1097/MOT.0b013e32832c58f1.
Donor reactive regulatory T cells (Treg) play an important role in tolerance induction and maintenance in experimental transplant models. In this review we focus on the formation of the donor reactive Treg pool and explore the potential of these cells for therapeutic application in clinical transplantation.
Donor reactive Treg can arise by both conversion of alloreactive nonregulatory cells and expansion of naturally occurring Treg (nTreg) cross-reactive with donor alloantigen but the quantitative contribution of each of these pathways is at present unclear. However, the fact that donor reactive Treg can be driven both in vivo and ex vivo by alloantigen challenge of nonregulatory precursors is encouraging as it demonstrates that the functional potential of these cells for use in clinical transplantation will not be limited by fortuitous cross-reactivity between nTreg and donor alloantigens. Treg can be generated in vivo by transplantation or alloantigen challenge in combination with Treg-permissive immunosuppression, or ex vivo by phenotypic selection or by polyclonal or antigen-specific stimulation. A number of ex-vivo protocols exist for the enrichment of Treg in the laboratory and in many cases these cells have demonstrable function both in vitro and in relevant graft-versus-host disease (GVHD) or organ transplant models. The challenge now is to understand the clinical opportunities and limitations that these populations present.
Combined with appropriate immunosuppression, Treg generated/expanded in vivo or ex vivo may hold the final key to operational tolerance in clinical setting.
供体反应性调节性T细胞（Treg）在实验性移植模型的免疫耐受诱导和维持中发挥重要作用。在本综述中，我们聚焦于供体反应性Treg库的形成，并探讨这些细胞在临床移植中治疗应用的潜力。
供体反应性Treg可通过同种异体反应性非调节性细胞的转化以及与供体同种异体抗原交叉反应的天然Treg（nTreg）的扩增产生，但目前尚不清楚每条途径的定量贡献。然而，非调节性前体细胞经同种异体抗原刺激可在体内和体外驱动供体反应性Treg这一事实令人鼓舞，因为这表明这些细胞在临床移植中的功能潜力不会受到nTreg与供体同种异体抗原之间偶然交叉反应的限制。Treg可通过移植或同种异体抗原刺激联合允许Treg的免疫抑制在体内产生，或通过表型选择、多克隆或抗原特异性刺激在体外产生。实验室中有多种体外方案用于富集Treg，在许多情况下，这些细胞在体外以及相关的移植物抗宿主病（GVHD）或器官移植模型中都具有可证明的功能。现在面临的挑战是了解这些细胞群体所带来的临床机遇和局限性。
与适当的免疫抑制相结合，体内或体外产生/扩增的Treg可能是临床实现免疫耐受的最终关键。
