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器官移植中的耐受原性树突状细胞治疗。

Tolerogenic dendritic cell therapy in organ transplantation.

机构信息

INSERM UMR1064, Center for Research in Transplantation and Immunology, Nantes, France.

CHU de Nantes, Institut de Transplantation Urologie Nephrologie (ITUN), Nantes, France.

出版信息

Transpl Int. 2017 Aug;30(8):754-764. doi: 10.1111/tri.12889. Epub 2016 Dec 19.

Abstract

Although the occurrence of acute rejection was significantly reduced and the allograft survival at 1 year was massively improved by the development of pharmacological immunosuppressive drugs, little progress has been made regarding long-term graft survival. Cell therapy appears to be an innovative and promising strategy to minimize the use of immunosuppression in transplantation and consequently increases long-term graft survival. The strength of cell therapy is that it will induce graft-specific tolerance and not a general immunosuppression of the patients. Several candidates, such as tolerogenic dendritic cells, have been gaining interest as an efficient means of promoting antigen-specific tolerance over recent years. Studies performed in rodent models have demonstrated the feasibility and efficacy of tolerogenic dendritic cells for the induction of tolerance in transplantation. In parallel, protocols to generate human tolerogenic dendritic cells in vitro have been defined, and some phase I clinical trials in autoimmune diseases have been recently performed to evaluate the safety of tolerogenic dendritic cell therapy. In this review, we will focus on the potential therapeutic interest of these cells in transplantation as well as their generation and characterization in humans. Finally, we will describe our current clinical trial using autologous tolerogenic dendritic cells in transplantation.

摘要

尽管通过开发药理学免疫抑制剂,急性排斥反应的发生率显著降低,并且移植物 1 年存活率得到了极大改善,但移植物的长期存活率几乎没有提高。细胞治疗似乎是一种创新且有前途的策略,可以减少移植中免疫抑制剂的使用,从而提高移植物的长期存活率。细胞治疗的优势在于,它将诱导移植物特异性耐受,而不是对患者进行一般性免疫抑制。近年来,一些候选细胞,如耐受性树突状细胞,作为促进抗原特异性耐受的有效手段引起了人们的兴趣。在啮齿动物模型中进行的研究表明,耐受性树突状细胞在诱导移植中的耐受性方面具有可行性和有效性。与此同时,已经确定了体外生成人源耐受性树突状细胞的方案,并且最近已经进行了一些针对自身免疫性疾病的 I 期临床试验,以评估耐受性树突状细胞治疗的安全性。在这篇综述中,我们将重点介绍这些细胞在移植中的潜在治疗意义,以及它们在人类中的生成和特征。最后,我们将描述我们目前在移植中使用自体耐受性树突状细胞的临床试验。

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