| First Author | Nguyen QP | Year | 2023 |
| Journal | Sci Immunol | Volume | 8 |
| Issue | 83 | Pages | eabq7486 |
| PubMed ID | 37172104 | Mgi Jnum | J:359630 |
| Mgi Id | MGI:7788533 | Doi | 10.1126/sciimmunol.abq7486 |
| Citation | Nguyen QP, et al. (2023) Transcriptional programming of CD4(+) T(RM) differentiation in viral infection balances effector- and memory-associated gene expression. Sci Immunol 8(83):eabq7486 |
| abstractText | 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(RM)), the developmental origins and transcriptional regulation of CD4(+) T(RM) remain largely undefined. Here, we investigated the phenotypic, functional, and transcriptional profiles of CD4(+) T(RM) in the small intestine (SI) responding to acute viral infection, revealing a shared gene expression program and chromatin accessibility profile with circulating T(H)1 and the progressive acquisition of a mature T(RM) program. Single-cell RNA sequencing identified heterogeneity among established CD4(+) T(RM), 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(H)1-associated Blimp1 and Id2 and T(FH)-associated Bcl6 were required for early T(RM) formation and development of a mature T(RM) population in the SI. These results demonstrate a developmental relationship between T(H)1 effector cells and the establishment of early T(RM), as well as highlighted differences in CD4(+) versus CD8(+) T(RM) populations, providing insights into the mechanisms underlying the origins, differentiation, and persistence of CD4(+) T(RM) in response to viral infection. |
