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CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance

Author

Listed:
  • Yuhong Chen

    (Blood Research Institute, Versiti)

  • Mei Yu

    (Blood Research Institute, Versiti)

  • Yongwei Zheng

    (Blood Research Institute, Versiti)

  • Guoping Fu

    (Blood Research Institute, Versiti)

  • Gang Xin

    (Blood Research Institute, Versiti)

  • Wen Zhu

    (Blood Research Institute, Versiti
    Medical College of Wisconsin)

  • Lan Luo

    (Blood Research Institute, Versiti
    Chinese PLA General Hospital)

  • Robert Burns

    (Blood Research Institute, Versiti)

  • Quan-Zhen Li

    (University of Texas Southwestern Medical Center)

  • Alexander L. Dent

    (Indiana University School of Medicine)

  • Nan Zhu

    (Blood Research Institute, Versiti)

  • Weiguo Cui

    (Blood Research Institute, Versiti)

  • Laurent Malherbe

    (Toxicology Division, Eli Lilly)

  • Renren Wen

    (Blood Research Institute, Versiti)

  • Demin Wang

    (Blood Research Institute, Versiti
    Medical College of Wisconsin
    Fujian Normal University)

Abstract

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ T follicular helper (Tfh) cells are the main subset regulating autoreactive B cells. Here we report a CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively modulated by Stat5. These CD8+ Tfh cells regulate the germinal center B cell response and control autoantibody production, as deficiency of Stat5 in CD8 T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and concomitant autoantibody production. CD8+ Tfh cells share similar gene signatures with CD4+ Tfh, and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study thus highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance.

Suggested Citation

  • Yuhong Chen & Mei Yu & Yongwei Zheng & Guoping Fu & Gang Xin & Wen Zhu & Lan Luo & Robert Burns & Quan-Zhen Li & Alexander L. Dent & Nan Zhu & Weiguo Cui & Laurent Malherbe & Renren Wen & Demin Wang, 2019. "CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance," Nature Communications, Nature, vol. 10(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:10:y:2019:i:1:d:10.1038_s41467-019-12446-5
    DOI: 10.1038/s41467-019-12446-5
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    Cited by:

    1. Bonnie Huang & James D. Phelan & Silvia Preite & Julio Gomez-Rodriguez & Kristoffer H. Johansen & Hirofumi Shibata & Arthur L. Shaffer & Qin Xu & Brendan Jeffrey & Martha Kirby & Stacie Anderson & Yan, 2022. "In vivo CRISPR screens reveal a HIF-1α-mTOR-network regulates T follicular helper versus Th1 cells," Nature Communications, Nature, vol. 13(1), pages 1-16, December.

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