EL-4：Immunologic Perspectives on Type I Diabetes

Jeenan Tseng, Ph.D.

Department of Microbiology and Tropical Medicine

George Washington University Medical Center

Washington, DC

e-mail: jeenan.tseng@sbcglobal.net

It is generally accepted that Type I diabetes is a progressive autoimmune disease.  In the active early stage of the disease, the autoimmunity is manifested by the destruction of b cells of the islet of Langerhans in the pancreas.  Several mechanisms may contribute to b cell destruction: (1) delayed type hypersensitivity reactions mediated by CD4⁺ T cells reactive with islet cell antigens, (2) cytotoxic T cells mediated lysis of islet cells, (3) local production of cytokines that directly or indirectly damage islet cells, and (4) auto-antibodies against islet cells.  All these mechanisms appear to be initiated by autoimmune reactive cells, which appear and are activated when the immunologic tolerance breaks down.  The susceptibility to the development of Type I diabetes are controlled by a large number of genes.  Several factors may contribute to the susceptibility: (1) unusual variants of MHC class II genes and common variants of MHC class I genes, (2) products of non-MHC genes such as IL-2 gene and insulin gene with tandem repeats in the promoter region, and (3) infectious and non-infectious agents such as viruses, toxins, cow milk, and possibly bacterial superantigens as well as botanicals that have strong immune-enhancing capabilities.  The susceptibility correlates well with the activation of autoimmunity to b cells.  Altogether, this immunologic information may be useful for development of effective vaccines, drugs, and reagents for rapid diagnosis of the disease at early stages.