Journal article
CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer
Immunity (Cambridge, Mass.), Vol.51(6), pp.1028-1042.e4
12/17/2019
DOI: 10.1016/j.immuni.2019.10.009
PMCID: PMC6929322
PMID: 31810883
Abstract
Although CD4+ T cell “help” is crucial to sustain antiviral immunity, the mechanisms by which CD4+ T cells regulate CD8+ T cell differentiation during chronic infection remain elusive. Here, using single-cell RNA sequencing, we show that CD8+ T cells responding to chronic infection were more heterogeneous than previously appreciated. Importantly, our findings uncovered the formation of a CX3CR1-expressing CD8+ T cell subset that exhibited potent cytolytic function and was required for viral control. Notably, our data further demonstrate that formation of this cytotoxic subset was critically dependent on CD4+ T cell help via interleukin-21 (IL-21) and that exploitation of this developmental pathway could be used therapeutically to enhance the killer function of CD8+ T cells infiltrated into the tumor. These findings uncover additional molecular mechanisms of how “CD4+ T cell help” regulates CD8+ T cell differentiation during persistent infection and have implications toward optimizing the generation of protective CD8+ T cells in immunotherapy.
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•scRNA-seq unveils a unique subset of cytolytic CD8+ T cells during chronic infection•CX3CR1+ CD8+ T cells are required to control chronic viral infection•CD4+ T cell help via IL-21 production is critical for CX3CR1+ CD8+ T cell formation•IL-21-producing CD4+ T cells enhance CX3CR1+ TIL formation and tumor control
The mechanisms by which CD4+ T cell help sustains exhausted CD8+ T cells during chronic infection have remained elusive. Here, Zander and colleagues show that CD4+ T-cell-derived IL-21 is required for the formation of a distinct subset of cytolytic CX3CR1+CD8+ T cells that protect against chronic infection and cancer.
Details
- Title: Subtitle
- CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer
- Creators
- Ryan Zander - Versiti Blood Center of WisconsinDavid Schauder - Medical College of WisconsinGang Xin - Versiti Blood Center of WisconsinChristine Nguyen - Medical College of WisconsinXiaopeng Wu - Versiti Blood Center of WisconsinAllan Zajac - University of Alabama at BirminghamWeiguo Cui - Versiti Blood Center of Wisconsin
- Resource Type
- Journal article
- Publication Details
- Immunity (Cambridge, Mass.), Vol.51(6), pp.1028-1042.e4
- DOI
- 10.1016/j.immuni.2019.10.009
- PMID
- 31810883
- PMCID
- PMC6929322
- NLM abbreviation
- Immunity
- ISSN
- 1074-7613
- eISSN
- 1097-4180
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: NIH, award: AI125741, DK108557; DOI: 10.13039/100000048, name: American Cancer Society; name: A Healthier Wisconsin; DOI: 10.13039/100000884, name: Cancer Research Institute; name: The Elizabeth Elser Doolittle Postdoctoral Fellowship; DOI: 10.13039/100000057, name: NIGMS, award: T32-GM080202
- Language
- English
- Date published
- 12/17/2019
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984297426402771
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