Development of new strategies to prevent type diabetes:: the role of animal models

Type 1 diabetes is an immune-mediated disease typically preceded by a long preclinical stage during which a growing number of islet-cell-specific autoantibodies appear in the serum. Although antigen-specific T lymphocytes and cytokines rather than these autoantibodies are the likely executors of beta-cell-destruction, these autoantibodies reflect the existence of autoimmunity that targets islet beta-cells. Abrogation of this autoimmunity during the preclinical stage would be the key to the prevention of type 1 diabetes. However, the quest of protecting islet-cells from the immune attack requires detailed knowledge of mechanisms that control islet-inflammation and beta-cell-destruction, and of mechanisms that control immune tolerance to peripheral self-antigens in general. This knowledge can only be obtained through further innovative research in experimental animal models. In this review, we will first examine how research in non-obese diabetic mice has already led to promising new strategies of diabetes prevention now being tested in human clinical trials. Thereafter, we will discuss how recent advances in understanding the mechanisms that control immune response to peripheral self-antigens such as beta-cell antigens may help to develop even more selective and effective strategies to prevent diabetes in the future.