Two major events contribute to the pathogenesis of autoimmune diseases such as Type 1 Diabetes (T1D): persistance of autoreactive T cells that are not deleted in the thymus and defects of immunoregulatory mechanisms. Our goal is to understand how immunoregulatory T cells downmodulate T cell-autoimmunity and to restore their defective function in autoimmune-prone individuals. We developed specific transgenic animal models to recruit regulatory T cell subsets to the target site of autoimmunity and investigate their key role in prevention of autoimmune diabetes.