CXCR5+PD-1+CD8+ T cells are a novel T helper cell sublineage and are negatively regulated by Stat5 [scRNA-Seq]

Many autoimmune diseases are characterized by the production of autoantibodies. The current view is that CD4+ Tfh cells are the main subset regulating autoreactive B cells. Here, we discover a distinct novel CXCR5+PD1+ Tfh subset of CD8+ T cells whose development and function are negatively regulated by Stat5. These CD8+ Tfh cells regulate the GC B cell response and control autoantibody production. Deficiency of Stat5 in CD8+ T cells leads to an increase of CD8+ Tfh cells, resulting in the breakdown of B cell tolerance and autoantibody production. CD8+ Tfh share similar gene signatures with CD4+ Tfh and require CD40L/CD40 and TCR/MHCI interactions to deliver help to B cells. Our study highlights the diversity of follicular T cell subsets that contribute to the breakdown of B-cell tolerance Splenic CXCR5+PD-1+CD8+ T cells were sorted from LCMV-infected Stat5+/+CD8Cre and Stat5fl/-CD8Cre mice (Armstrong, day8) or from Stat5+/+CD8CreIgHELsHEL and Stat5fl/-CD8CreIgHELsHEL mice, and subjected to sc-RNA-seq analysis.