T-CELL RECOGNITION OF BETA-CELL AUTOANTIGENS IN INSULIN-DEPENDENT DIABETES-MELLITUS

Autoimmune beta-cells reactive to beta-cell autoantigens are generally believed to play an essential role in the immune-mediated selective p ancreatic islet beta-cell destruction process leading to insulin-depen dent diabetes mellitus (IDDM). Many of the supportive data have been o btained from animal models of this disease, but often these data remai n to be validated in human IDDM, including the nature of the responsib le autoreactive T cells and their targets on the beta cells. In the la st few years, however, considerable progress has been made, and severa l candidate autoantigens have been identified. Diabetogenic T-cell clo nes have been isolated and characterized in animal models, but for the majority of these clones, the target autoantigen is unknown. In human s, the first islet autoantigens recognized by autoreactive T cells hav e been defined. This opens the way to designing immunointerventive str ategies selective for these T cells and their candidate target antigen s, in an attempt to prevent the onset of IDDM. In this review, we desc ribed the significance of T lymphocytes for the pathogenic process lea ding to type 1 diabetes and our studies showing (auto)immune responses by beta-cell-reactive T lymphocytes of newly diagnosed patients.