Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.
Strength of tonic T cell receptor signaling instructs T follicular helper cell-fate decisions.
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DOI：
10.1038/s41590-020-0781-7
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发表时间：
2020-11
影响因子：
30.5
通讯作者：
Allen PM
中科院分区：
文献类型：
--
作者：
Bartleson JM;Viehmann Milam AA;Donermeyer DL;Horvath S;Xia Y;Egawa T;Allen PM
T滤泡辅助细胞（Tfh）在对病原体和疫苗的适应性免疫反应中至关重要；然而，是什么推动了他们的发展计划的启动仍不清楚。研究表明，T细胞抗原受体（TCR）依赖的机制可能负责最早的tfh命运决定，但TCR的一个关键方面被忽视了：补性TCR信号。我们假设滋补信号影响Tfh细胞的早期发育。在这里，两个小鼠tcr转基因CD4+ T细胞，LLO56和LLO118，识别相同的抗原- pmhc，但经历不同强度的强直信号，显示低强直信号促进Tfh细胞分化。多克隆T细胞与这些发现相似，具有初始Nur77表达区分Tfh潜能。同时生成两种小鼠品系，强直信号强度增加和减少，直接建立了强直信号强度与Tfh发育的反比关系。我们的研究结果阐明了强直性TCR信号在早期tfh谱系决定中的核心作用。
T follicular helper (Tfh) cells are critical in adaptive immune responses to pathogens and vaccines; however, what drives initiation of their developmental program remains unclear. Studies suggest a T cell antigen receptor (TCR)-dependent mechanism may be responsible for the earliest Tfh-fate decision, but a critical aspect of the TCR has been overlooked: tonic TCR signaling. We hypothesized tonic signaling influences early Tfh cell development. Here, two murine TCR-transgenic CD4+ T cells, LLO56 and LLO118, that recognize the same antigenic-pMHC 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 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 development. Our findings elucidate a central role for tonic TCR signaling in early Tfh-lineage decisions.
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影响因子：
30.5
作者：
通讯作者：
--
影响因子：
32.4
作者：
Choi YS;Kageyama R;Eto D;Escobar TC;Johnston RJ;Monticelli L;Lao C;Crotty S
通讯作者：
Crotty S
影响因子：
8.8
作者：
Myers DR;Lau T;Markegard E;Lim HW;Kasler H;Zhu M;Barczak A;Huizar JP;Zikherman J;Erle DJ;Zhang W;Verdin E;Roose JP
通讯作者：
Roose JP
影响因子：
56.9
作者：
FungLeung, WP;Surh, CD;Karlsson, L
通讯作者：
Karlsson, L
DOI：
10.1073/pnas.1000966107
发表时间：
2010-05-11
影响因子：
11.1
作者：
Govern, Christopher C.;Paczosa, Michelle K.;Husebyb, Eric S.
通讯作者：
Husebyb, Eric S.