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PREVENTION OF TYPE 1 DIABETES

1998; Elsevier BV; Volume: 82; Issue: 4 Linguagem: Inglês

10.1016/s0025-7125(05)70022-5

1557-9859

Alex Rabinovitch, Jay S. Skyler,

Pancreatic function and 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.