INSULIN-DEPENDENT DIABETES-MELLITUS IN THE NONOBESE DIABETIC MOUSE - A DISEASE MEDIATED BY T-CELL ANERGY

The non-obese diabetic (NOD) mouse spontaneously develops autoimmune t ype I insulin-dependent diabetes mellitus (IDDM) with a similar immuno pathological profile to the human disease. Development of the disease in both the NOD mouse and in humans is under polygenic control and inf luenced by many environmental factors. Diabetes results from a specifi c T cell-mediated destruction of pancreatic insulin-producing islet be ta cells. Both CD4 and CD8 T cells as well as macrophages are required for the development of diabetes in NOD mice. An intriguing similarity between murine and human diabetes is a T cell proliferative unrespons iveness (anergy) that may be a susceptibility factor to disease onset. Defective communication between antigen-presenting cells (APC) and T cells, and/or an aberrant production or activity of inflammatory cytok ines (e.g. chemokines) in the thymus and periphery (e.g. pancreas) may account for the unresponsiveness of regulatory T cells leading to a l oss of immunological tolerance to beta cell autoantigens in NOD mice a nd in diabetic humans.