Regulatory T cells (Tregs) are thought to be pivotal in controlling both autoimmune and allogeneic undesired immune responses. Recently, an extensive effort has been devoted to design clinical trials with Tregs in T cell-mediated diseases (such as autoimmune diseases or transplantation). Theoretically, this approach can be used also in patients with autoimmunity (e.g., type 1 diabetes) undergoing allogeneic transplantation (e.g., pancreatic islet transplant). However, in this latter case Tregs must control two distinct effector immune responses: a pre-existing response towards self-antigens and a de novo response induced by the newly transplanted allogeneic cells. In this review we summarize results supporting the use of Tregs in controlling either autoimmunity or allo-transplantation. We also provide our view on how Treg therapy can achieve the final goal of immunological tolerance in the extremely challenging clinical setting of type 1 diabetic subjects transplanted with allogeneic islets.
