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

doi:10.1038/s41467-019-12446-5

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 journal › Article › peer-review

53 Scopus citations

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 language	English (US)
Article number	4415
Journal	Nature communications
Volume	10
Issue number	1
DOIs	https://doi.org/10.1038/s41467-019-12446-5
State	Published - Dec 1 2019
Externally published	Yes

ASJC Scopus subject areas

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

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10.1038/s41467-019-12446-5

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title = "CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance",

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.",

author = "Yuhong Chen and Mei Yu and Yongwei Zheng and Guoping Fu and Gang Xin and Wen Zhu and Lan Luo and Robert Burns and Li, {Quan Zhen} and Dent, {Alexander L.} and Nan Zhu and Weiguo Cui and Laurent Malherbe and Renren Wen and Demin Wang",

note = "Funding Information: This work is supported in part by NIH grants AI079087 (D.W.), HL130724 (D.W.), AI125741 (W.C.) and AI132771 (A.L.D.). Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

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doi = "10.1038/s41467-019-12446-5",

language = "English (US)",

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AU - Chen, Yuhong

AU - Yu, Mei

AU - Zheng, Yongwei

AU - Fu, Guoping

AU - Xin, Gang

AU - Zhu, Wen

AU - Luo, Lan

AU - Burns, Robert

AU - Li, Quan Zhen

AU - Dent, Alexander L.

AU - Zhu, Nan

AU - Cui, Weiguo

AU - Malherbe, Laurent

AU - Wen, Renren

AU - Wang, Demin

PY - 2019/12/1

Y1 - 2019/12/1

N2 - 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.

AB - 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.

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

Abstract

ASJC Scopus subject areas

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