The role of T-cells in the pathogenesis of Type 1 diabetes: from cause to cure.
Type 1 diabetes mellitus results from a T-cell mediated autoimmune destruction of the pancreatic beta cells in genetically predisposed individuals. The knowledge of the immunopathogenesis has increased enormously in the last two decades. The contribution of T-cells in the pathogenesis is beyond doubt. Therapies directed against T-cells have been shown to halt the disease process and prevent recurrent beta-cell destruction after islet transplantation. Less is known about the nature and function of these T-cells, the cause of the loss of tolerance to islet autoantigens, why the immune system apparently fails to suppress autoreactivity, and whether (or which) autoantigen(s) are critically involved in the initiation or progression of the disease. The contribution of dendritic cells in directing the immune response is clear, while the contribution of B-cells and autoantibodies is subject to reconsideration. Autoreactive T-cells have proven to be valuable tools to study pathogenic or diabetes-related processes. Measuring T-cell autoreactivity has also provided critical information to determine the fate of islet allografts transplanted to Type 1 diabetic patients. Cellular autoimmunity is a difficult study subject, but it has been a worthwhile quest to unravel the role of T-cells in the pathogenesis of Type 1 diabetes. The challenge for the future is to determine which factors contribute to the loss of tolerance to beta-cell antigens, and to define what measures T-cells can provide to suppress autoreactivity, since it is becoming increasingly evident that T-cells provide a two-edged sword: some T-cells could be pathogenic, but others can regulate the disease process and thus form new targets for immunointervention.
Roep
Bart O
BO
Dept. Immunohaematology and Blood Transfusion, E3-Q, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands. boroep@lumc.nl
D000818:Animals; D015551:Autoimmunity / Q000276:immunology; D002999:Clone Cells; D016207:Cytokines / Q000502:physiology; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000473:pathology* / Q000628:therapy; D004777:Environment; D006801:Humans; D007515:Islets of Langerhans / Q000473:pathology; D051379:Mice; D013601:T-Lymphocytes / Q000502:physiology*
D016207:Cytokines