A historical view from thirty eventful years of immunotherapy in autoimmune diabetes.

Type 1 diabetes is an autoimmune disease. It was thus logical to attempt preventing or stopping the progression of the disease by immunotherapy. Following the strategies used in organ transplantation, the first trials in the 80s used cyclosporin in patients presenting recently diagnosed Type 1 diabetes. The effect was spectacular but waned when the treatment was stopped as the effect was non antigen-specific. Going back from bed to bench-side major efforts were then devoted to device strategies allowing induction or restoration of self-tolerance. Two major approaches provided encouraging results when used in spontaneous models of autoimmune diabetes that are the use of β-cell autoantigens and of monoclonal antibodies to CD3. Based on these results academic phase II trials and subsequently pharmaceutically driven phase III trials were launched. Results are now available and when critically analyzed in the frame of these last three decades they provide support to the possibility of making step by step immunotherapy available to all new onset diabetic patients with a hope of inducing long-term remission of the disease if the treatment is started sufficiently early, immediately after diagnosis.