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.

Details

Title
CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance
Author
Chen, Yuhong 1 ; Yu, Mei 1 ; Zheng, Yongwei 1 ; Fu, Guoping 1 ; Xin, Gang 1 ; Zhu, Wen 2   VIAFID ORCID Logo  ; Luo, Lan 3 ; Burns, Robert 1 ; Quan-Zhen, Li 4 ; Dent, Alexander L 5 ; Zhu, Nan 1 ; Cui, Weiguo 1   VIAFID ORCID Logo  ; Malherbe, Laurent 6 ; Wen, Renren 1 ; Wang, Demin 7   VIAFID ORCID Logo 

1  Blood Research Institute, Versiti, Milwaukee, WI, USA 
2  Blood Research Institute, Versiti, Milwaukee, WI, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA 
3  Blood Research Institute, Versiti, Milwaukee, WI, USA; Chinese PLA General Hospital, Beijing, China 
4  Department of Immunology and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, USA 
5  Department of Microbiology and Immunology, Indiana University School of Medicine, Indianapolis, IN, USA 
6  Toxicology Division, Eli Lilly, Indianapolis, IN, USA 
7  Blood Research Institute, Versiti, Milwaukee, WI, USA; Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, WI, USA; Biomedical Research Center of South China, College of Life Sciences, Fujian Normal University, Fuzhou, Fujian, China 
Pages
1-15
Publication year
2019
Publication date
Sep 2019
Publisher
Nature Publishing Group
e-ISSN
20411723
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41467-019-12446-5
ProQuest document ID
2298761636
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.