Approaches to type 1 diabetes prevention by intervention in cytokine immunoregulatory circuits.
Type 1 (insulin-dependent) diabetes mellitus, like other organ specific autoimmune diseases, results from a disorder of immunoregulation. T cells specific for pancreatic islet beta cell constituents (autoantigens) exist normally but are restrained by regulatory mechanisms (self-tolerant state). When regulation fails, beta cell-specific autoreactive T cells become activated and expand clonally. Current evidence indicates that islet beta cell-specific autoreactive T cells belong to a T helper 1 (Th1) subset, and these Th1 cells and their characteristic cytokine products, IFNgamma and IL-2, are believed to cause islet inflammation (insulitis) and beta cell destruction. Immune-mediated destruction of beta cells precedes hyperglycemia and clinical symptoms by many years because these become apparent only when most of the insulin-secreting beta cells have been destroyed. Therefore, several approaches are being tested or are under consideration for clinical trials to prevent or arrest complete autoimmune destruction of islet beta cells and insulin-dependent diabetes. Approaches that attempt to correct underlying immunoregulatory defects in autoimmune diabetes include interventions aimed at i) deleting beta cell autoreactive Th1 cells and cytokines (IFNgamma and IL-2) and/or ii) increasing regulatory Th2 cells and/or Th3 cells and their cytokine products (IL-4, IL-10 and TGFbeta1).
D000818:Animals; D015551:Autoimmunity; D016207:Cytokines / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control*; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D016207:Cytokines