GSE131345
A dormant T cell population with autoimmune potential exhibits low self-reactivity and infiltrates islets in type I diabetes
T cells have been established as the key drivers of autoimmune diabetes. However, it is unknown whether all T cells that infiltrate the pancreas are equally pathogenic, and how the level of reactivity for self-antigen modulates differentiation and pathogenic potential of effector T cells.  Moreover, the contribution of bystander, non-antigen reactive T cells in islet autoimmunity has not been resolved. Using multi-color flow cytometry in combination with Nur77-GFP reporter of TCR signaling we identified a “dormant” population of CD4+ T cells that infiltrate the islets of pre-diabetic NOD mice and constitute a significant proportion of all islet infiltrating T cells (~47%). We analyzed TCR repertoire, transcriptional profile, effector function, and autoimmune potential of this subpopulation. This T cell population, characterized by low level expression of CD5 and a unique TCR repertoire, exhibited central memory phenotype with reduced activation and effector function; however, induced rapid diabetes upon transfer. Overall, our study suggests that the strength of reactivity for tissue antigen dictates the level of T cell activation and differentiation; however, cells with low level of TCR signaling and reactivity for islet antigen infiltrating the pancreas of NOD mice are pathogenic and are capable of inducing beta cell destruction. Overall design: 2 Islet Teff Hi samples, 2 Islet Teff low samples. Compared also to samples submitted in GEO GSE102231 and GSE106467