用于免疫耐受的T细胞基因工程

Genetic Engineering of T Cells for Immune Tolerance.

作者信息

Scott David W

机构信息

Department of Medicine, Uniformed Services University of Health Sciences, Bethesda, MD 20814, USA.

出版信息

Mol Ther Methods Clin Dev. 2019 Dec 24;16:103-107. doi: 10.1016/j.omtm.2019.11.022. eCollection 2020 Mar 13.

DOI:10.1016/j.omtm.2019.11.022

PMID:31934598

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6953701/

Abstract

Regulatory T cells (Tregs) play a role in the induction and maintenance of tolerance, as well as in modulating aberrant immune responses. While expanded Tregs have been used in clinical trials, they are polyclonal and the frequency of specific Tregs is very low. To overcome this issue, we have endeavored to "specify" Tregs by engineering them to express receptors that can recognize a given antigen and applied this protocol in autoimmunity, hemophilia and allergy. Thus, we have used retroviral transduction of a specific T cell receptor, single-chain variable fragments (Fvs), or antigen domains in Tregs to achieve this goal. This review summarizes our steps to achieve the ultimate goal of modulating human diseases.

摘要

调节性T细胞（Tregs）在诱导和维持免疫耐受以及调节异常免疫反应中发挥作用。虽然扩增后的Tregs已用于临床试验，但它们是多克隆的，特定Tregs的频率非常低。为了克服这个问题，我们努力通过对Tregs进行工程改造，使其表达能够识别特定抗原的受体来“特异性地”改造Tregs，并将该方案应用于自身免疫性疾病、血友病和过敏症。因此，我们利用逆转录病毒转导特定的T细胞受体、单链可变片段（Fvs）或Tregs中的抗原结构域来实现这一目标。本综述总结了我们为实现调节人类疾病这一最终目标所采取的步骤。