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CD4+ T Cell Help Is Required for the Formation of a Cytolytic CD8+ T Cell Subset that Protects against Chronic Infection and Cancer.

Authors
  • Zander, Ryan1
  • Schauder, David2
  • Xin, Gang1
  • Nguyen, Christine2
  • Wu, Xiaopeng1
  • Zajac, Allan3
  • Cui, Weiguo4
  • 1 Blood Research Institute, BloodCenter of Wisconsin, Milwaukee, WI 53213, USA.
  • 2 Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
  • 3 Department of Microbiology, University of Alabama at Birmingham, Birmingham, AL 35233, USA.
  • 4 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]
Type
Published Article
Journal
Immunity
Publication Date
Dec 03, 2019
Identifiers
DOI: 10.1016/j.immuni.2019.10.009
PMID: 31810883
Source
Medline
Keywords
Language
English
License
Unknown

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. Copyright © 2019 Elsevier Inc. All rights reserved.

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