美国华盛顿大学Hao Yuan Kueh、Junyue Cao以及Jay Shendure研究组合作发现，可逆的、可调的表观遗传沉默TCF1在T细胞记忆决策中产生灵活性。2024年1月31日出版的《免疫》杂志发表了这项成果。

通过使用时间分辨转录组学、定量活成像和急性感染模型在单细胞和克隆谱系水平上跟踪CD8+ T细胞，他们发现T细胞在抗原识别后会早期维持或失去记忆潜能。然而，在病原体清除后，T细胞可能会重新获得最初丢失的记忆潜力。从机制上讲，这种灵活性是通过随机顺式表观遗传开关实现的，该开关可调且可逆地使记忆调节因子TCF1沉默，以响应刺激。

数学模型显示了这种灵活性如何允许记忆T细胞数量，与病原体毒力和免疫反应的大小进行稳健的缩放。他们认为，细胞决策的灵活性和随机性确保了对各种威胁的最佳免疫反应。

据介绍，免疫系统通过其形成的记忆细胞的数量和类型，来编码有关病原威胁严重程度的信息。这种编码来自淋巴细胞在挑战过程中，维持或失去自我更新和记忆潜力的决定。

附：英文原文

Title: Reversible, tunable epigenetic silencing of TCF1 generates flexibility in the T cell memory decision

Author: Kathleen Abadie, Elisa C. Clark, Rajesh M. Valanparambil, Obinna Ukogu, Wei Yang, Riza M. Daza, Kenneth K.H. Ng, Jumana Fathima, Allan L. Wang, Judong Lee, Tahseen H. Nasti, Avinash Bhandoola, Armita Nourmohammad, Rafi Ahmed, Jay Shendure, Junyue Cao, Hao Yuan Kueh

Issue&Volume: 2024-01-31

Abstract: The immune system encodes information about the severity of a pathogenic threat inthe quantity and type of memory cells it forms. This encoding emerges from lymphocytedecisions to maintain or lose self-renewal and memory potential during a challenge.By tracking CD8+ T cells at the single-cell and clonal lineage level using time-resolved transcriptomics,quantitative live imaging, and an acute infection model, we find that T cells willmaintain or lose memory potential early after antigen recognition. However, followingpathogen clearance, T cells may regain memory potential if initially lost. Mechanistically,this flexibility is implemented by a stochastic cis-epigenetic switch that tunably and reversibly silences the memory regulator, TCF1,in response to stimulation. Mathematical modeling shows how this flexibility allowsmemory T cell numbers to scale robustly with pathogen virulence and immune responsemagnitudes. We propose that flexibility and stochasticity in cellular decisions ensureoptimal immune responses against diverse threats.

DOI: 10.1016/j.immuni.2023.12.006

Source: https://www.cell.com/immunity/fulltext/S1074-7613(23)00537-X