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移植中的调节性 T 细胞治疗:概述。

Treg therapy in transplantation: a general overview.

机构信息

Immunoregulation Laboratory, Division of Transplantation Immunology & Mucosal Biology, MRC Centre for Transplantation, King's College London, Guy's Hospital, London, UK.

School of Health Sport and Bioscience, University of East London, London, UK.

出版信息

Transpl Int. 2017 Aug;30(8):745-753. doi: 10.1111/tri.12909. Epub 2017 Feb 6.

Abstract

Solid organ transplantation remains the treatment of choice for end-stage organ failure. Whilst the short-term outcomes post-transplant have improved in the last decades, chronic rejection and immunosuppressant side effects remain an ongoing concern. Hematopoietic stem cell transplantation is a well-established procedure for the treatment of patients with haematological disorders. However, donor T cells are continually primed and activated to react against the host causing graft-versus-host disease (GvHD) that leads to tissue damages and death. Regulatory T cells (Tregs) play an essential role in maintaining tolerance to self-antigens, preventing excessive immune responses and abrogating autoimmunity. Due to their suppressive properties, Tregs have been extensively studied for their use as a cellular therapy aiming to treat GvHD and limit immune responses responsible for graft rejection. Several clinical trials have been conducted or are currently ongoing to investigate safety and feasibility of Treg-based therapy. This review summarizes the general understanding of Treg biology and presents the methods used to isolate and expand Tregs. Furthermore, we describe data from the first clinical trials using Tregs, explaining the limitations and future application of these cells.

摘要

实体器官移植仍然是治疗终末期器官衰竭的首选方法。尽管在过去几十年中,移植后的短期结果有所改善,但慢性排斥反应和免疫抑制剂的副作用仍然是一个持续存在的问题。造血干细胞移植是治疗血液系统疾病患者的一种成熟方法。然而,供体 T 细胞不断被激活以对抗宿主,导致移植物抗宿主病(GvHD),从而导致组织损伤和死亡。调节性 T 细胞(Tregs)在维持对自身抗原的耐受性、防止过度免疫反应和消除自身免疫方面发挥着重要作用。由于其抑制特性,Tregs 已被广泛研究用于细胞治疗,旨在治疗 GvHD 并限制导致移植物排斥的免疫反应。已经进行了或正在进行几项临床试验,以研究基于 Treg 的治疗的安全性和可行性。本综述总结了 Treg 生物学的一般认识,并介绍了用于分离和扩增 Treg 的方法。此外,我们描述了使用 Tregs 的首批临床试验数据,解释了这些细胞的局限性和未来应用。

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