Type 1 diabetes (T1D) is the result of a T-lymphocyte–dependent autoimmune process that specifically destroys the insulin-secreting beta-cells of the pancreas. To down-modulate T cell responses and re-establish immunological self-tolerance to the beta-islets is fundamental for the definitive cure of T1D. Immunological tolerance can be achieved by the induction of Ag-specific T regulatory cells (Tregs) that suppress effector T cells specific for pancreatic beta-islets, while leaving the rest of the immune system intact. The main goals of the laboratory are to characterize the autoimmune responses occurring in T1D patients and to define new approaches for re-establishing self-tolerance.