Treg-based immunotherapy for antigen-specific immune suppression and stable tolerance induction: a perspective.

IF 4.1 Q2 IMMUNOLOGY

Immunotherapy advances Pub Date : 2023-01-01 DOI:10.1093/immadv/ltad007

Shimon Sakaguchi, Ryoji Kawakami, Norihisa Mikami

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Abstract

FoxP3-expressing regulatory T cells (Tregs), whether naturally generated in the immune system or unnaturally induced from conventional T cells (Tconvs) in the laboratory, have much therapeutic value in treating immunological diseases and establishing transplantation tolerance. Natural Tregs (nTregs) can be selectively expanded in vivo by administration of low-dose IL-2 or IL-2 muteins for immune suppression. For adoptive Treg cell therapy, nTregs can be expanded in vitro by strong antigenic stimulation in the presence of IL-2. Synthetic receptors such as CAR can be expressed in nTregs to equip them with a particular target specificity for suppression. In addition, antigen-specific Tconvs can be converted in vitro to functionally stable Treg-like cells by a combination of antigenic stimulation, FoxP3 induction, and establishment of the Treg-type epigenome. This review discusses current and prospective strategies for Treg-based immune suppression and the issues to be resolved for achieving stable antigen-specific immune suppression and tolerance induction in the clinic by targeting Tregs.

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基于treg的免疫疗法对抗原特异性免疫抑制和稳定耐受诱导的研究进展

表达foxp3的调节性T细胞(Tregs)，无论是在免疫系统中自然产生的，还是在实验室中由常规T细胞(Tconvs)非自然诱导的，在治疗免疫性疾病和建立移植耐受方面都具有很大的治疗价值。天然Tregs (nTregs)可以通过低剂量的IL-2或IL-2突变蛋白在体内选择性扩增来抑制免疫。对于过继性Treg细胞治疗，在IL-2存在的情况下，ntreg可以通过强抗原刺激在体外扩增。合成受体如CAR可以在ntreg中表达，使它们具有特定的抑制靶标特异性。此外，抗原特异性Tconvs可以通过抗原刺激、FoxP3诱导和treg型表观基因组的建立相结合，在体外转化为功能稳定的treg样细胞。本文综述了目前和未来基于treg的免疫抑制策略，以及在临床上通过靶向treg实现稳定的抗原特异性免疫抑制和耐受诱导需要解决的问题。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Immunotherapy advances

CiteScore

5.00

自引率

0.00%

发文量

审稿时长

7 weeks