Insulin-Specific Tolerance in Diabetes

At present it is possible to predict the development of type 1A diabetes (immune-mediated diabetes) in man and prevent the disorder in animals. Studies of immunity to insulin play a prominent role in both disease prediction and disease prevention. For both man and the NOD mouse, insulin autoantibodies usually precede the development of diabetes and can be utilized to assist in disease prediction. T cells clones recognizing insulin, both CD4 and CD8, can transfer disease to young mice or immunodeficient animals. Specific insulin peptides reacting with these clones have been identified, their crystal structure when bound to a human “diabetogenic” MHC allele has been determined, and specific peptides can be used either to induce or to prevent disease. Clinical trials of both insulin and an altered peptide ligand of insulin to prevent islet β-cell destruction are underway. Insulin is one of a number of islet autoantigens, but it is likely that immune responses to insulin will be central to both pathogenesis and immunologic protection.