Self-Reactivity and T-Cell Receptor Repertoire of Effector and Regulatory T Cells in Autoimmune Diabetes

T cell infiltration and accumulation in pancreatic islets during autoimmune diabetes is to a large degree driven by TCR reactivity to beta cell antigens. However, it is not fully clear whether the strength of TCR reactivity to beta cell antigens is an important determinant of effector or regulatory T cell function. We observed that CD5 expression is proportional to the level of self-reactivity based on Nur77-GFP reporter of TCR signaling and insulin tetramer staining of islet infiltrating T cells. Using RNAseq profiling, TCR sequencing, and cell transfer we show that CD5 segregates functionally and transcriptionally distinct effector and regulatory T cells, demonstrating that reactivity to beta cell antigens is an important determinant of effector and regulatory T cell function in autoimmune diabetes.