Summer Research Description: Approximately 1.25 million Americans today are living with type 1 diabetes (T1D), and an estimated 40,000 more are diagnosed annually. T1D occurs when an individual develops autoimmunity against insulin-producing islet cells, leading to islet destruction and an inability to produce insulin. One promising avenue towards a cure is transplanting islet grafts while also inducing sustainable and permanent immune system tolerance to the graft. Long-term graft tolerance is prevented by both the alloimmune response to the foreign graft, and the reoccurring, tissue-specific autoimmune response. Tolerance induction has been achieved in B6 (wild type) mice through use of tolerance-inducing drug therapy; however, this has not been achieved in autoimmune strains such as the NOD (diabetic prone) or SLE123 (lupus prone). It is believed that a crucial component in autoimmunity is an inability for immune regulatory cells to suppress immune effector cells responsible for islet destruction. We will further our understanding of cellular and molecular interactions underlying autoimmunity through use of genetic and pharmacologic approaches and gain greater insight into the activation, migration, and action of immune regulatory cells. Overall, discovering how the autoimmune environment varies from the non-autoimmune could be key to long-term islet graft transplantation tolerance in individuals with T1D.