Prevention of type 1 diabetes.
This article discusses type 1 diabetes mellitus, which results from insulin deficiency caused by autoimmune destruction of the insulin-producing beta-cells in the pancreatic islets of Langerhans. The autoimmune response against islet beta-cells is believed to result from a disorder of immunoregulation. According to this concept, T lymphocytes (T cells) autoreactive to certain beta-cell constituents exist normally but are restrained by regulatory (suppressor) T cells. Activation of beta-cell autoreactive T cells together with deficient regulatory T cell responses is believed to result in clonal expansion of autoreactive T cells, and these cells may elicit a cascade of beta-antigen specific (T cell) immune and nonspecific inflammatory responses that destroy islet beta-cells. Islet beta-cells autoreactive T cells seem to secrete type 1 cytokines, whereas regulatory T cells may secrete type 2 and type 3 cytokines; therefore, type 1 diabetes may result from a relative dominance of type 1 cytokines over type 2 and type 3 cytokines. These concepts derive mainly from studies in animal models with spontaneous autoimmune diabetes, and the evidence in humans with type 1 diabetes is sparse. Nevertheless, the concept of type 1 diabetes as a disorder of immunoregulation has spurred clinical trials of diabetes prevention based on strategies directed at diverting the immune response from autoimmunity to self-tolerance, for example, by administration of beta-cell autoantigens, and by attempting to tip the immune balance in favor of the production or action of type 2 and type 3 cytokines over type 1 cytokines.
Department of Medicine, University of Alberta, Edmonton, Canada.
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A
Rabinovitch
J S
JS
Skyler
D000818:Animals; D001324:Autoantigens / Q000276:immunology / Q000627:therapeutic use; D001327:Autoimmune Diseases / Q000276:immunology / Q000517:prevention & control; D015551:Autoimmunity; D016207:Cytokines / Q000145:classification / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000517:prevention & control*; D004195:Disease Models, Animal; D006801:Humans; D007108:Immune Tolerance; D007328:Insulin / Q000172:deficiency; D007515:Islets of Langerhans / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology
D001324:Autoantigens; D016207:Cytokines; D007328:Insulin