PROTECTIVE AND DESTRUCTIVE EFFECTS OF MICROBIAL INFECTION IN INSULIN-DEPENDENT DIABETES-MELLITUS

Insulin-dependent diabetes mellitus (IDDM) is a T-cell mediated autoim mune disease, which results in the destruction of the islet beta-cells . The major histocompatibility complex (MHC) encodes the major suscept ibility gene in IDDM. The concordance rate for diabetes in identical t wins is 30-50% and in inbred animal models of disease the incidence ra te is 20-80%. These results emphasize a role for environmental factors in the disease process. It has long been suggested that IDDM in human s may be caused by viral infections. While considerable progress has b een made in defining the genetics of IDDM, our understanding of the ro le of environmental factors, which might provide a more direct approac h 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 effecto r or protective T cells in IDDM.