CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer.
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53213, USA.
Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53213, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA. Electronic address: [email protected]
- Published Article
- Publication Date
Dec 03, 2019
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. Copyright © 2019 Elsevier Inc. All rights reserved.
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This record was last updated on 12/31/2019 and may not reflect the most current and accurate biomedical/scientific data available from NLM.
The corresponding record at NLM can be accessed at https://www.ncbi.nlm.nih.gov/pubmed/31810883