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

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

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Article number4415
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

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T-cells
Helper-Inducer T-Lymphocytes
B-Lymphocytes
Cells
Autoantibodies
T-Lymphocyte Subsets
set theory
cells
CD40 Ligand
Germinal Center
breakdown
Autoimmune Diseases
Genes
T-Lymphocytes
genes
signatures

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

Cite this

Chen, Y., Yu, M., Zheng, Y., Fu, G., Xin, G., Zhu, W., ... Wang, D. (2019). CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance. Nature communications, 10(1), [4415]. https://doi.org/10.1038/s41467-019-12446-5

CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance. / Chen, Yuhong; Yu, Mei; Zheng, Yongwei; Fu, Guoping; Xin, Gang; Zhu, Wen; Luo, Lan; Burns, Robert; Li, Quan Zhen; Dent, Alexander L.; Zhu, Nan; Cui, Weiguo; Malherbe, Laurent; Wen, Renren; Wang, Demin.

In: Nature communications, Vol. 10, No. 1, 4415, 01.12.2019.

Research output: Contribution to journalArticle

Chen, Y, Yu, M, Zheng, Y, Fu, G, Xin, G, Zhu, W, Luo, L, Burns, R, Li, QZ, Dent, AL, Zhu, N, Cui, W, Malherbe, L, Wen, R & Wang, D 2019, 'CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance', Nature communications, vol. 10, no. 1, 4415. https://doi.org/10.1038/s41467-019-12446-5
Chen, Yuhong ; Yu, Mei ; Zheng, Yongwei ; Fu, Guoping ; Xin, Gang ; Zhu, Wen ; Luo, Lan ; Burns, Robert ; Li, Quan Zhen ; Dent, Alexander L. ; Zhu, Nan ; Cui, Weiguo ; Malherbe, Laurent ; Wen, Renren ; Wang, Demin. / CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance. In: Nature communications. 2019 ; Vol. 10, No. 1.
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