Nature communications. 2019-09-27; 10.1: 4415.

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

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

PMID: 31562329


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 CXCR5PD1 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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