Transcriptional programming of CD4 + T RM differentiation in viral infection balances effector- and memory-associated gene expression

After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 tissue-resident memory T cells (T ), the developmental origins and transcriptional regulation of CD4 T remain lar...

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Published inScience immunology Vol. 8; no. 83; p. eabq7486
Main Authors Nguyen, Quynh P, Takehara, Kennidy K, Deng, Tianda Z, O'Shea, Shannon, Heeg, Maximilian, Omilusik, Kyla D, Milner, J Justin, Quon, Sara, Pipkin, Matthew E, Choi, Jinyong, Crotty, Shane, Goldrath, Ananda W
Format Journal Article
LanguageEnglish
Published United States 26.05.2023
Subjects
CD4-Positive T-Lymphocytes
Cell Differentiation
Gene Expression
Humans
Immunologic Memory
Virus Diseases
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Summary:After resolution of infection, T cells differentiate into long-lived memory cells that recirculate through secondary lymphoid organs or establish residence in tissues. In contrast to CD8 tissue-resident memory T cells (T ), the developmental origins and transcriptional regulation of CD4 T remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4 T in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T 1 and the progressive acquisition of a mature T program. Single-cell RNA sequencing identified heterogeneity among established CD4 T , which were predominantly located in the lamina propria, and revealed a population of cells that coexpressed both effector- and memory-associated genes, including the transcriptional regulators Blimp1, Id2, and Bcl6. T 1-associated Blimp1 and Id2 and T -associated Bcl6 were required for early T formation and development of a mature T population in the SI. These results demonstrate a developmental relationship between T 1 effector cells and the establishment of early T , as well as highlighted differences in CD4 versus CD8 T populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4 T in response to viral infection.
ISSN:2470-9468
DOI:10.1126/sciimmunol.abq7486