1. CXCR5+PD-1+ follicular helper CD8 T cells control B cell tolerance.
- Author
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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, and Wang, Demin
- Subjects
T helper cells ,B cells ,T cells ,ANTIBODY formation ,GERMINAL centers - 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. B cell response and antibody production are generally facilitated by CD4+ follicular helper (Tfh) cells. Here the authors identify a subset of CXCR5+ PD1+ CD8+ Tfh cells that is normally suppressed by STAT5 signaling, so that STAT5 deficiency in mice increases the number of these CD8+ Tfh cells and induces concomitant production of autoantibodies. [ABSTRACT FROM AUTHOR]- Published
- 2019
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