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

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 generation of Tex cells is unclear. Single-cel...

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Vydané v:	Immunity (Cambridge, Mass.) Ročník 51; číslo 5; s. 840
Hlavní autori:	Chen, Zeyu, Ji, Zhicheng, Ngiow, Shin Foong, Manne, Sasikanth, Cai, Zhangying, Huang, Alexander C, Johnson, John, Staupe, Ryan P, Bengsch, Bertram, Xu, Caiyue, Yu, Sixiang, Kurachi, Makoto, Herati, Ramin S, Vella, Laura A, Baxter, Amy E, Wu, Jennifer E, Khan, Omar, Beltra, Jean-Christophe, Giles, Josephine R, Stelekati, Erietta, McLane, Laura M, Lau, Chi Wai, Yang, Xiaolu, Berger, Shelley L, Vahedi, Golnaz, Ji, Hongkai, Wherry, E John
Médium:	Journal Article
Jazyk:	English
Vydavateľské údaje:	United States 19.11.2019
Predmet:	Animals CD8-Positive T-Lymphocytes - immunology CD8-Positive T-Lymphocytes - metabolism Cell Differentiation - genetics Cell Differentiation - immunology Chronic Disease Gene Expression Profiling Gene Regulatory Networks Host-Pathogen Interactions - genetics Host-Pathogen Interactions - immunology Mice Programmed Cell Death 1 Receptor - metabolism T Cell Transcription Factor 1 - genetics T Cell Transcription Factor 1 - metabolism Transcription, Genetic Virus Diseases - genetics Virus Diseases - immunology Virus Diseases - virology chronic infection immunotherapy CD8 T cell exhaustion exhaustion cancer transcriptional circuit PD-1
ISSN:	1097-4180, 1097-4180
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Shrnutí:	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 generation of Tex cells is unclear. Single-cell RNA sequencing (scRNA-seq) and lineage tracing identified a TCF-1 Ly108 PD-1 CD8 T cell population that seeds development of mature Tex cells early during chronic infection. TCF-1 mediated the bifurcation between divergent fates, repressing development of terminal KLRG1 effectors while fostering KLRG1 Tex precursor cells, and PD-1 stabilized this TCF-1 Tex precursor cell pool. TCF-1 mediated a T-bet-to-Eomes transcription factor transition in Tex precursors by promoting Eomes expression and drove c-Myb expression that controlled Bcl-2 and survival. These data define a role for TCF-1 in early-fate-bifurcation-driving Tex precursor cells and also identify PD-1 as a protector of this early TCF-1 subset.
Bibliografia:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1097-4180 1097-4180
DOI:	10.1016/j.immuni.2019.09.013