Sir William Dunn School, University of Oxford, Oxford, OX13RE, UK.
Eur J Immunol. 2021 Jul;51(7):1580-1591. doi: 10.1002/eji.202048795. Epub 2021 May 16.
The field of tissue transplantation has revolutionized the treatment of patients with failing organs. Its success, thus far, has depended on combinations of immunosuppressive drugs that damp host immunity, while also imposing numerous unwanted side-effects. There is a longstanding recognition that better treatment outcomes, will come from replacing these drugs, fully or in part, by taking advantage of tractable physiological mechanisms of self-tolerance. The past 50 years have seen many advances in the field of self-tolerance, but perhaps, the most tractable of these has been the more recent discovery of a subset T-cells (Treg) whose role is to regulate or damp immunity. This article is intended to first provide the reader with some historical background to explain why we have been slow to identify these cells, despite numerous clues to their existence, and also to indicate how little we know about how they achieve their regulatory function in averting transplant rejection. However, as is often the case in immunology, the therapeutic needs often dictate that our advances move to translation even before detailed explanations of the science are available. The final part of the article will briefly summarize how Treg are being harnessed as agents to interface with or perhaps, replace current drug combinations.
组织移植领域已经彻底改变了衰竭器官患者的治疗方法。迄今为止，其成功依赖于免疫抑制药物的组合，这些药物抑制了宿主的免疫反应，同时也带来了许多不必要的副作用。人们早就认识到，更好的治疗效果将来自于利用可控制的自身耐受生理机制，部分或全部替代这些药物。在过去的 50 年中，自身耐受领域取得了许多进展，但也许其中最具可操作性的是最近发现了一类 T 细胞（Treg），其作用是调节或抑制免疫。本文首先旨在为读者提供一些历史背景，以解释为什么尽管有许多关于这些细胞存在的线索，但我们一直未能识别出这些细胞，同时也表明我们对它们如何实现其在避免移植排斥中的调节功能知之甚少。然而，正如免疫学中经常发生的那样，治疗需求通常要求我们即使在科学解释可用之前，也将进展推向转化。本文的最后一部分将简要总结如何利用 Treg 作为与当前药物组合相互作用或替代的药物。
