Autoimmune CD4 T cells maintain function and survive in chronic autoimmunity by restricting terminal differentiation (NOD)

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: Single cell ATACseq/RNAseq analysis was performed using 10X Multiome kit. TCR+ cells were sorted from non-draining lymph nodes and pancreatic islets of two 10-week-old NOD female mice