Journal article
Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
Immunity (Cambridge, Mass.), Vol.55(3), pp.475-493.e5
03/08/2022
DOI: 10.1016/j.immuni.2022.01.018
PMCID: PMC8916994
PMID: 35216666
Abstract
CD4+ T cell-derived interleukin 21 (IL-21) sustains CD8+ T cell responses during chronic viral infection, but the helper subset that confers this protection remains unclear. Here, we applied scRNA and ATAC-seq approaches to determine the heterogeneity of IL-21+CD4+ T cells during LCMV clone 13 infection. CD4+ T cells were comprised of three transcriptionally and epigenetically distinct populations: Cxcr6+ Th1 cells, Cxcr5+ Tfh cells, and a previously unrecognized Slamf6+ memory-like (Tml) subset. T cell differentiation was specifically redirected toward the Tml subset during chronic, but not acute, LCMV infection. Although this subset displayed an enhanced capacity to accumulate and some developmental plasticity, it remained largely quiescent, which may hinder its helper potential. Conversely, mixed bone marrow chimera experiments revealed that Tfh cell-derived IL-21 was critical to sustain CD8+ T cell responses and viral control. Thus, strategies that bolster IL-21+Tfh cell responses may prove effective in enhancing CD8+ T cell-mediated immunity.
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•scRNA-seq reveals heterogeneity among IL-21+ CD4+ T cells during chronic LCMV infection•Differential expression of CXCR6 and CXCR5 defines three distinct CD4+ T cell subsets•Chronic LCMV infection redirects CD4+ T cell differentiation toward a memory-like subset•Tfh-derived IL-21 critically sustains effector CD8+ T cell development and viral control
CD4+ T cell help via IL-21 production is critical to sustain CD8+ T cell responses during chronic viral infection, but whether a particular subset mediates this process remains unclear. Zander et al. identify heterogeneity among IL-21-producing CD4+ T cells during chronic infection and find that Tfh-derived IL-21 promotes effector CD8+ T cell development and antiviral immunity.
Details
- Title: Subtitle
- Tfh-cell-derived interleukin 21 sustains effector CD8+ T cell responses during chronic viral infection
- Creators
- Ryan Zander - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAMoujtaba Y. Kasmani - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAYao Chen - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAPaytsar Topchyan - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAJian Shen - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAShikan Zheng - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USARobert Burns - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USAJennifer Ingram - University of Alabama at BirminghamCan Cui - Yale School of MedicineNikhil Joshi - Yale School of MedicineJoseph Craft - Yale School of MedicineAllan Zajac - University of Alabama at BirminghamWeiguo Cui - Blood Research Institute, Versiti Wisconsin, Milwaukee, WI 53226, USA
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.55(3), pp.475-493.e5
- DOI
- 10.1016/j.immuni.2022.01.018
- PMID
- 35216666
- PMCID
- PMC8916994
- NLM abbreviation
- Immunity
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Publisher
- Elsevier Inc
- Language
- English
- Date published
- 03/08/2022
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297318702771
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