補體T細胞受體信號影響卵泡輔助性T細胞的命運決定

補體T細胞受體信號影響卵泡輔助性T細胞的命運決定

作者：

小柯機器人

發布時間：2020/9/30 15:08:09

補體T細胞受體信號的強度決定了卵泡輔助性T細胞（T_FH）的命運，這一成果由美國華盛頓大學醫學院Paul M. Allen研究組經過不懈努力而取得。這一研究成果於2020年9月28日發表在《自然-免疫學》上。

研究人員認為補體信號影響了早期T_FH細胞的發育。研究人員利用兩個鼠類T細胞抗原受體（TCR）轉基因CD4⁺ T細胞系LLO56和LLO118發現低補體信號可促進T_FH細胞分化；LLO56和LLO118能夠識別主要組織相容性複合物分子呈遞的相同抗原肽，但產生不同的補體信號強度。多克隆T細胞與這些發現相符，起始Nur77表達可區分T_FH細胞的分化潛能。

研究人員還利用兩個增加和降低補體信號強度的小鼠品系來建立補體信號強度與T_FH細胞發育之間的逆向關係。該發現闡明了補品TCR信號在早期T_FH細胞譜系決定中的核心作用。

據介紹，卵泡輔助性T細胞在對病原體和疫苗的適應性免疫反應中至關重要。然而，誘導其發育起始的分子機制尚不清楚。研究表明，TCR依賴性機制可能最早決定了T_FH細胞的命運，但是該理論忽略了TCR的一個關鍵方面：補體TCR信號的傳導。

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