Autoimmune CD4 T cells maintain function and survive in chronic autoimmunity by restricting terminal differentiation
The mechanisms behind survival of autoimmune CD4 T cells during chronic stimulation are unclear. Examining early time-points during T cell priming showed that activation of autoimmune CD4 T cells in the absence of infectious signals allowed maintenance of TCF1 expression, albeit at reduced levels. Tcf7 locus was epigenetically modified in circulating autoimmune CD4 T cells, suggesting a pre-programmed de novo methylation of the locus in early stages of autoimmune CD4 T cell differentiation which mirrored the epigenetic profile of recently recruited CD4 CD62L+ T cells in the tissue.  Collectively, the data presented here show that the unique environment during autoimmune CD4 T cell priming allows T cells to finetune TCF1 expression to maintain long-term survival and function. Overall design: pancreatic islets, spleen+non-draining lymph nodes were harvested from BDC2.5 transferred cells into congenically labelled NOD mice. BDC2.5 CD4+Vb4 cells were sorted and subjected to 10X multiome scATAC/Gene expression sequncing