美国宾夕法尼亚大学的E. John Wherry研究团队发现，以TCF-1为中心的转录网络驱动一个效应子与衰竭CD8 T细胞的命运决定。2019年11月19日出版的《免疫》杂志发表了这一成果。

TCF-1是祖细胞衰竭CD8 T细胞（Tex）中的关键转录因子。此外，该Tex细胞亚群介导了对PD-1检查点途径拮抗的应答。但是，转录因子TCF-1在早期命运决定和Tex细胞初始生成中的作用尚不清楚。

单细胞RNA测序（scRNA-seq）和谱系追踪鉴定了TCF-1 + Ly108 + PD-1 + CD8 T细胞群体，该群体在慢性感染的早期就开始产生成熟Tex细胞。TCF-1介导不同命运之间的分歧，抑制末端KLRG1Hi效应子的发展，同时产生KLRG1Lo Tex前体细胞，PD-1稳定了该TCF-1 + Tex前体细胞库。TCF-1通过促进Eomes表达并驱动控制Bcl-2和存活的c-Myb表达，在Tex前体中介导T-bet-to-Eomes转录因子过渡。

这些数据定义了TCF-1在早期分歧驱动Tex前体细胞中的作用，并且还确定了PD-1是该早期TCF-1亚群的保护者。

附：英文原文

Title: TCF-1-Centered Transcriptional Network Drives an Effector versus Exhausted CD8 T Cell-Fate Decision

Author: Zeyu Chen, Zhicheng Ji, Shin Foong Ngiow, Sasikanth Manne, Zhangying Cai, Alexander C. Huang, John Johnson, Ryan P. Staupe, Bertram Bengsch, Caiyue Xu, Sixiang Yu, Makoto Kurachi, Ramin S. Herati, Laura A. Vella, Amy E. Baxter, Jennifer E. Wu, Omar Khan, Jean-Christophe Beltra, Josephine R. Giles, Erietta Stelekati, Laura M. McLane, Chi Wai Lau, Xiaolu Yang, Shelley L. Berger, Golnaz Vahedi, Hongkai Ji, E. John Wherry

Issue&Volume: 2019/11/19

Abstract: TCF-1 is a key transcription factor in progenitor exhausted CD8 T cells (Tex). Moreover,this Tex cell subset mediates responses to PD-1 checkpoint pathway blockade. However,the role of the transcription factor TCF-1 in early fate decisions and initial generationof Tex cells is unclear. Single-cell RNA sequencing (scRNA-seq) and lineage tracingidentified a TCF-1+Ly108+PD-1+ CD8 T cell population that seeds development of mature Tex cells early during chronicinfection. TCF-1 mediated the bifurcation between divergent fates, repressing developmentof terminal KLRG1Hi effectors while fostering KLRG1Lo Tex precursor cells, and PD-1 stabilized this TCF-1+ Tex precursor cell pool. TCF-1 mediated a T-bet-to-Eomes transcription factor transitionin Tex precursors by promoting Eomes expression and drove c-Myb expression that controlledBcl-2 and survival. These data define a role for TCF-1 in early-fate-bifurcation-drivingTex precursor cells and also identify PD-1 as a protector of this early TCF-1 subset.

DOI: 10.1016/j.immuni.2019.09.013

Source: https://www.cell.com/immunity/fulltext/S1074-7613(19)30409-1