德国亚琛工业大学Oliver Pabst、Moritz Muschaweck等研究人员合作揭示发炎结肠中CD4⁺ T细胞受体库的改变。这一研究成果于2021年9月27日在线发表在国际学术期刊《免疫》上。

为了明确T细胞受体库和肠道抗原环境的相互关系，研究人员追踪了过继转移的T细胞群。结果表明，主导的TCRα克隆型在产生干扰素-γ和白细胞介素-17的T细胞之间共享，但不包括调节性Foxp3⁺ T细胞。相同的TCRα克隆型在不同个体的结肠中积累，而抗生素或确定的定植与不同的T细胞克隆型扩张相关。这些结果证明了肠道CD4⁺ T细胞激活的关键方面，并表明在结肠炎期间，少数微生物物种对肠道T细胞组合发挥了主导作用。研究人员推测，优势的促炎症T细胞克隆可能为人类炎症性肠病提供一个治疗靶标。

据了解，肠道T细胞的关键方面，包括它们的抗原特异性和它们被微生物群和其他肠道抗原的选择，以及单个T细胞克隆对调节和效应功能的贡献，仍未得到解决。

附：英文原文

Title: Cognate recognition of microbial antigens defines constricted CD4+ T cell receptor repertoires in the inflamed colon

Author: Moritz Muschaweck, Lydia Kopplin, Fabio Ticconi, Angela Schippers, Aida Iljazovic, Eric J.C. Gálvez, Ali T. Abdallah, Norbert Wagner, Ivan G. Costa, Till Strowig, Oliver Pabst

Issue&Volume: 2021-09-27

Abstract: Key aspects of intestinal T cells, including their antigen specificity and their selection by the microbiota and other intestinal antigens, as well as the contribution of individual T cell clones to regulatory and effector functions, remain unresolved. Here we tracked adoptively transferred T cell populations to specify the interrelation of T cell receptor repertoire and the gut antigenic environment. We show that dominant TCRα clonotypes were shared between interferon-γ- and interleukin-17-producing but not regulatory Foxp3+ T cells. Identical TCRα clonotypes accumulated in the colon of different individuals, whereas antibiotics or defined colonization correlated with the expansion of distinct expanded T cell clonotypes. Our results demonstrate key aspects of intestinal CD4+ T cell activation and suggest that few microbial species exert a dominant effect on the intestinal T cell repertoire during colitis. We speculate that dominant proinflammatory T cell clones might provide a therapeutic target in human inflammatory bowel disease.

DOI: 10.1016/j.immuni.2021.08.014

Source: https://www.cell.com/immunity/fulltext/S1074-7613(21)00346-0