Immunobiology and Transplant Science Center and Department of Surgery, Houston Methodist Hospital, Texas Medical Center, Houston, TX, USA.
Department of Surgery, Weill Cornell Medical College of Cornell University, New York, NY, USA.
Adv Exp Med Biol. 2021;1278:273-287. doi: 10.1007/978-981-15-6407-9_14.
Organ transplantation is a preferred treatment option for patients with end-stage organ failure. However, transplant induces a robust rejection response that necessitates life-long immunosuppression, which often leads to a plethora of comorbidities. Thus, the goal of transplantation is to achieve a state of tolerance wherein the host permanently accepts the transplanted organ while maintaining normal immune responses to other antigens. Regulatory T cells (Tregs) play an important role in realizing this goal and are being explored in both animal models and human clinical trials. In this chapter, we discuss the key principles of transplant rejection and Treg biology, as well as the status of human clinical trials utilizing Tregs as cellular therapy. We discuss how the current immunosuppressive drugs are utilized in transplantation in favoring an increased Treg to T effector cell ratio, different approaches in generation of therapeutic Tregs, and various facets in Treg trial designs in the clinic. Such clinical trials provided many opportunities to leverage our understanding of Tregs in transplantation. They also demonstrated Tregs as a safe cellular therapy for human use, but the efficacy of this treatment has yet to be fully realized.
器官移植是治疗终末期器官衰竭患者的首选治疗方法。然而，移植会引起强烈的排斥反应，需要终身免疫抑制，这往往会导致多种并发症。因此，移植的目标是实现一种耐受状态，即宿主永久性地接受移植器官，同时对其他抗原保持正常的免疫反应。调节性 T 细胞（Treg）在实现这一目标中发挥着重要作用，目前正在动物模型和人类临床试验中进行探索。在本章中，我们讨论了移植排斥和 Treg 生物学的关键原则，以及利用 Treg 作为细胞疗法的人类临床试验的现状。我们讨论了目前在移植中使用的免疫抑制药物如何有利于增加 Treg 与 T 效应细胞的比例，生成治疗性 Treg 的不同方法，以及临床试验中 Treg 试验设计的各个方面。这些临床试验为我们利用 Tregs 在移植中的理解提供了许多机会。它们还证明了 Treg 是一种安全的用于人体的细胞疗法，但这种治疗的疗效尚未完全实现。
