Commentary - Autoimmunity and diabetes

The face of immune-mediated (type 1) diabetes is changing. No longer consid ered a disease confined to childhood, the incidence rate in Western countri es is clearly rising and affecting younger children. Such a secular trend c an only be explained on the basis of increased contacts with adverse enviro nmental factors acting on a background of complex genetics. Multiple defect s in immunological tolerance to "self" predispose to immune-mediated (type 1) diabetes. Initiation of immune responses involves the cytokine rich natu ral killer T cells. Such cells appear deficient in both humans and the rode nt models of the disease. Furthermore, the regulatory abilities of T cells in general seem to be compromised. Effector mechanisms probably are dominat ed by cell-mediated beta cell destruction through apoptosis induction. Surp risingly, the essential antigen-presenting cells in the autoimmune processe s involved appear to be beta lymphocytes. The improved understanding of the beta cell autoantigens involved has led to better disease prediction. The long prodromal phase now readily identifiable through autoantibodies is spa wning hopes of disease prevention, notably through antigen-based interventi ons or diabetes "vaccines."