Autoimmune disease results from the interplay between environmental and genetic factors. Recent studies indicated that autoimmune diseases like Type 1 Diabetes (T1D) are induced by genetic or environment-induced alterations of immune regulatory pathways whose function is to avoid or limit the activation/expansion of self-reactive T lymphocytes. Our objective is to determine whether a defect of immuneregulation underlies the pathogenesis of autoimmune diabetes in mice and humans and to restore those regulatory pathways for prevention/treatment of T1D.