Transcriptional programming of CD4+ TRM differentiation in viral infection balances effector- and memory-associated gene expression.
Sci Immunol
; 8(83): eabq7486, 2023 05 12.
Article
in En
| MEDLINE
| ID: mdl-37172104
ABSTRACT
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 (TRM), the developmental origins and transcriptional regulation of CD4+ TRM remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4+ TRM in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating TH1 and the progressive acquisition of a mature TRM program. Single-cell RNA sequencing identified heterogeneity among established CD4+ TRM, 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. TH1-associated Blimp1 and Id2 and TFH-associated Bcl6 were required for early TRM formation and development of a mature TRM population in the SI. These results demonstrate a developmental relationship between TH1 effector cells and the establishment of early TRM, as well as highlighted differences in CD4+ versus CD8+ TRM populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4+ TRM in response to viral infection.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Virus Diseases
/
Immunologic Memory
Type of study:
Risk_factors_studies
Limits:
Humans
Language:
En
Journal:
Sci Immunol
Year:
2023
Document type:
Article
Affiliation country:
Estados Unidos