补体T细胞受体信号的强度决定了卵泡辅助性T细胞（T_FH）的命运，这一成果由美国华盛顿大学医学院Paul M. Allen研究组经过不懈努力而取得。这一研究成果于2020年9月28日发表在《自然-免疫学》上。

研究人员认为补体信号影响了早期T_FH细胞的发育。研究人员利用两个鼠类T细胞抗原受体（TCR）转基因CD4⁺ T细胞系LLO56和LLO118发现低补体信号可促进T_FH细胞分化；LLO56和LLO118能够识别主要组织相容性复合物分子呈递的相同抗原肽，但产生不同的补体信号强度。多克隆T细胞与这些发现相符，起始Nur77表达可区分T_FH细胞的分化潜能。

研究人员还利用两个增加和降低补体信号强度的小鼠品系来建立补体信号强度与T_FH细胞发育之间的逆向关系。该发现阐明了补品TCR信号在早期T_FH细胞谱系决定中的核心作用。

据介绍，卵泡辅助性T细胞在对病原体和疫苗的适应性免疫反应中至关重要。然而，诱导其发育起始的分子机制尚不清楚。研究表明，TCR依赖性机制可能最早决定了T_FH细胞的命运，但是该理论忽略了TCR的一个关键方面：补体TCR信号的传导。

附：英文原文

Title: Strength of tonic T cell receptor signaling instructs T follicular helper cell–fate decisions

Author: Juliet M. Bartleson, Ashley A. Viehmann Milam, David L. Donermeyer, Stephen Horvath, Yu Xia, Takeshi Egawa, Paul M. Allen

Issue&Volume: 2020-09-28

Abstract: T follicular helper (TFH) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives the initiation of their developmental program remains unclear. Studies suggest that a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest TFH cell–fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized that tonic signaling influences early TFH cell development. Here, two murine TCR-transgenic CD4+ T cells, LLO56 and LLO118, which recognize the same antigenic peptide presented on major histocompatibility complex molecules but experience disparate strengths of tonic signaling, revealed low tonic signaling promotes TFH cell differentiation. Polyclonal T cells paralleled these findings, with naive Nur77 expression distinguishing TFH cell potential. Two mouse lines were also generated to both increase and decrease tonic signaling strength, directly establishing an inverse relationship between tonic signaling strength and TFH cell development. Our findings elucidate a central role for tonic TCR signaling in early TFH cell-lineage decisions. The pathways controlling T follicular helper (TFH) cell development are only partially understood. Allen and colleagues demonstrate the importance of the T cell receptor, with low tonic signaling promoting TFH cell development and high tonic signaling opposing it.

DOI: 10.1038/s41590-020-0781-7

Source: https://www.nature.com/articles/s41590-020-0781-7