Protective and destructive effects of microbial infection in insulin-dependent diabetes mellitus.
Insulin-dependent diabetes mellitus (IDDM) is a T-cell mediated autoimmune disease, which results in the destruction of the islet beta-cells. The major histocompatibility complex (MHC) encodes the major susceptibility gene in IDDM. The concordance rate for diabetes in identical twins is 30-50% and in inbred animal models of disease the incidence rate is 20-80%. These results emphasize a role for environmental factors in the disease process. It has long been suggested that IDDM in humans may be caused by-viral infections. While considerable progress has been made in defining the genetics of IDDM, our understanding of the role of environmental factors, which might provide a more direct approach to therapy is considerably lacking. We suggest that (1) the density and affinity of epitopes derived from microbial antigens that bind to MHC molecules; (2) their cross-reactivity with beta-cell antigens; and (3) the nature of immunoregulatory cytokines induced by the microbial infections are the primary factors in the induction of either effector or protective T cells in IDDM.
Singh
B
B
John P. Robarts Research Institute, University of Western Ontario, London, Canada.
Prange
S
S
Jevnikar
A M
AM
D000818:Animals; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control / Q000628:therapy / Q000821:virology*; D004777:Environment; D006801:Humans; D018716:Molecular Mimicry / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
D018089:Superantigens