Oral Insulin Treatment Suppresses Virus-induced Antigen-specific Destruction of b Cells and Prevents Autoimmune Diabetes in Transgenic Mice

Oral administration of self-antigens has been proposed as a therapy to prevent and treat autoimmune diseases. Here we report that oral treatment with insulin prevents virus-induced insulin-dependent diabetes mellitus (IDDM) in a transgenic (tg) mouse model. Such mice express the viral nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV) under control of the rat insulin promoter in their pancreatic b cells and , 2% spontaneously develop diabetes. However, 2 mo after challenge with LCMV, IDDM occurs in . 95% of tg mice but not in controls. Oral treatment with 1 mg of insulin twice per week for 2 mo starting either 1 wk before or 10 d after initiating LCMV infection prevents IDDM in . 50% of the tg mice (observation time 8 mo). Thus, insulin therapy is effective in preventing progression to overt IDDM in prediabetic tg mice with ongoing islet infiltration. Oral administration of insulin does not affect the generation of LCMV-NP–specific anti-self cytotoxic T lymphocytes nor the infiltration of lymphocytes into the pancreas. However, less b cells are destroyed in insulin-treated mice, upregulation of MHC class I and II molecules does not occur, and antiviral (self) cytotoxic T lymphocytes are not found in the islets, events present in tg mice developing IDDM. The majority of lymphocytes in the islets of insulin-treated tg mice without IDDM produces IL-4, IL-10, and TGFb . In contrast, lymphocytes from islets of tg mice developing IDDM mainly make g -IFN. ( J. Clin. Invest. 1996. 98:1324–1331.)