Transcriptional programming of CD4 + T RM differentiation in viral infection balances effector- and memory-associated gene expression.
Quynh P NguyenKennidy K TakeharaTianda Z DengShannon O'SheaMaximilian HeegKyla D OmilusikJ Justin MilnerSara QuonMatthew E PipkinJinyong ChoiShane CrottyAnanda W GoldrathPublished in: Science immunology (2023)
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.
Keyphrases
- gene expression
- single cell
- induced apoptosis
- transcription factor
- nk cells
- cell cycle arrest
- dna methylation
- dendritic cells
- computed tomography
- multiple sclerosis
- quality improvement
- patient safety
- oxidative stress
- intensive care unit
- high resolution
- magnetic resonance
- dna damage
- mass spectrometry
- cell proliferation
- extracorporeal membrane oxygenation
- liver failure
- immune response