Journal article
Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection
eLife, Vol.11, e80079
05/07/2022
DOI: 10.7554/eLife.80079
PMCID: PMC9629829
PMID: 36255051
Abstract
Although recent evidence indicates that CD4+ T cells responding to chronic viral infection are functionally heterogenous, our understanding of the developmental relationships between these subsets, and a determination of how their transcriptional landscape compares to their acute infection counterparts remains unclear. Additionally, whether cell-intrinsic factors such as TCR usage influence CD4+ T cell fate commitment during persistent infection has not previously been studied. Herein, we perform single-cell RNA sequencing (scRNA-seq) combined with single-cell T cell receptor sequencing (scTCR-seq) on virus-specific CD4+ T cells isolated from mice infected with chronic lymphocytic choriomeningitis virus (LCMV) infection. We identify several transcriptionally distinct states among the Th1, Tfh, and memory-like T cell subsets that form at the peak of infection, including the presence of a previously unrecognized Slamf7+ subset with cytolytic features. We further show that the relative distribution of these populations differs substantially between acute and persistent LCMV infection. Moreover, while the progeny of most T cell clones displays membership within each of these transcriptionally unique populations, overall supporting a one cell-multiple fate model, a small fraction of clones display a biased cell fate decision, suggesting that TCR usage may impact CD4+ T cell development during chronic infection. Importantly, comparative analyses further reveal both subset-specific and core gene expression programs that are differentially regulated between CD4+ T cells responding to acute and chronic LCMV infection. Together, these data may serve as a useful framework and allow for a detailed interrogation into the clonal distribution and transcriptional circuits underlying CD4+ T cell differentiation during chronic viral infection.
Details
- Title: Subtitle
- Delineating the transcriptional landscape and clonal diversity of virus-specific CD4+ T cells during chronic viral infection
- Creators
- Ryan ZanderAchia KhatunMoujtaba Y KasmaniYao ChenWeiguo Cui
- Resource Type
- Journal article
- Publication Details
- eLife, Vol.11, e80079
- DOI
- 10.7554/eLife.80079
- PMID
- 36255051
- PMCID
- PMC9629829
- NLM abbreviation
- Elife
- ISSN
- 2050-084X
- eISSN
- 2050-084X
- Grant note
- DOI: 10.13039/100000002, name: NIH NIAID, award: R01 AI125741; DOI: 10.13039/100000002, name: NIH NIAID, award: K99/R00 AI153537; DOI: 10.13039/100000002, name: NIH NIAID, award: R01 AI148403; DOI: 10.13039/100000002, name: NIH NIAID, award: DK127526; DOI: 10.13039/100000048, name: American Cancer Society; DOI: 10.13039/100000057, name: NIGMS, award: T32-GM080202
- Language
- English
- Date published
- 05/07/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984530378102771
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