小柯机器人

美国圣路易斯华盛顿大学Takeshi Egawa、斯坦福大学Ansuman T. Satpathy等研究人员合作发现，依赖BCL6的TCF-1⁺祖细胞维持效应型和辅助型CD4⁺T细胞对持久性抗原的反应。这一研究成果于2022年5月27日在线发表在国际学术期刊《免疫》上。

研究人员表示，激活后不久，CD4⁺T细胞被分离成BCL6⁺滤泡辅助（Tfh）和BCL6^-效应（Teff）T细胞。

研究人员利用小鼠慢性LCMV感染模型探讨了这些亚群在慢性抗原刺激期间是如何维持的。利用单细胞转录组和表观基因组分析，研究人员确定了一个具有记忆特征的PD-1⁺ TCF-1⁺ CD4⁺ T细胞群。TCR克隆追踪和过继转移实验表明，这些细胞具有自我更新能力，并继续产生Teff和Tfh细胞，从而作为祖细胞发挥作用。

条件性缺失实验显示，这些祖细胞的发展依赖于Bcl6，这对于维持抗原特异性CD4⁺T细胞对慢性感染的反应至关重要。一个类似的CD4⁺T细胞群在引流淋巴结中发展，从而应对肿瘤。这项研究揭示了CD4⁺T细胞在持续的抗原暴露过程中的异质性和可塑性，并强调了它们通过一种稳定的、双潜能的中间状态的群体动态。

附：英文原文

Title: BCL6-dependent TCF-1+ progenitor cells maintain effector and helper CD4+ T cell responses to persistent antigen

Author: Yu Xia, Katalin Sandor, Joy A. Pai, Bence Daniel, Saravanan Raju, Renee Wu, Sunnie Hsiung, Yanyan Qi, Tenzin Yangdon, Mariko Okamoto, Chun Chou, Kamir J. Hiam-Galvez, Robert D. Schreiber, Kenneth M. Murphy, Ansuman T. Satpathy, Takeshi Egawa

Issue&Volume: 2022-05-27

Abstract: Soon after activation, CD4+ T cells are segregated into BCL6+ follicular helper (Tfh) and BCL6– effector (Teff) T cells. Here, we explored how these subsets are maintained duringchronic antigen stimulation using the mouse chronic LCMV infection model. Using singlecell-transcriptomic and epigenomic analyses, we identified a population of PD-1+ TCF-1+ CD4+ T cells with memory-like features. TCR clonal tracing and adoptive transfer experimentsdemonstrated that these cells have self-renewal capacity and continue to give riseto both Teff and Tfh cells, thus functioning as progenitor cells. Conditional deletionexperiments showed Bcl6-dependent development of these progenitors, which were essentialfor sustaining antigen-specific CD4+ T cell responses to chronic infection. An analogous CD4+ T cell population developed in draining lymph nodes in response to tumors. Our studyreveals the heterogeneity and plasticity of CD4+ T cells during persistent antigen exposure and highlights their population dynamicsthrough a stable, bipotent intermediate state.

DOI: 10.1016/j.immuni.2022.05.003

Source: https://www.cell.com/immunity/fulltext/S1074-7613(22)00223-0

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