Chen, YuhongYu, MeiZheng, YongweiFu, GuopingXin, GangZhu, WenLuo, LanBurns, RobertLi, Quan-ZhenDent, Alexander L.Zhu, NanCui, WeiguoMalherbe, LaurentWen, RenrenWang, Demin2019-12-222019-12-222019-09-27Chen, 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. doi:10.1038/s41467-019-12446-5https://hdl.handle.net/1805/21549Many 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.en-USAntibodiesAutoimmunityGene regulation in immune cellsCD8-positive T cellsArticle