Oral administration of the immunodominant B-chain of insulin reduces diabetes in a co-transfer model of diabetes in the NOD mouse and is associated with a switch from Th1 to Th2 cytokines.

Important note: Information in this article was accurate in 1998. The state of the art may have changed since the publication date.

Oral administration of the immunodominant B-chain of insulin reduces diabetes in a co-transfer model of diabetes in the NOD mouse and is associated with a switch from Th1 to Th2 cytokines.

J Autoimmun. 1997 Aug;10(4):339-46. Unique Identifier : AIDSLINE /MED97383173
Polanski M; Melican NS; Zhang J; Weiner HL; Center for Neurologic Diseases, Brigham and Women's Hospital and; Harvard Medical School, Boston, MA, 02115, USA.

Abstract: Oral administration of antigen leads to systemic immune unresponsiveness. Low dose oral tolerance generates regulatory cells which, when triggered in an antigen-specific manner, suppress inflammatory responses. We have previously shown that oral administration of an organ-specific antigen, porcine insulin, protects against diabetes development in the NOD mouse. In the present study we extend these observations to the B-chain of insulin, a 30-amino-acid peptide which has now been shown by others to contain the immunogenic epitope. Oral administration of the B-chain slowed diabetes development in a co-transfer model in which cells from B-chain-fed animals were co-transferred with diabetogenic cells (P=0.02). Further exposure to antigen via feeding of the co-transfer recipient animals not only slowed diabetes development but prevented diabetes in some animals P=0.01). In vitro proliferation of popliteal lymph node cells from fed and immunized animals was suppressed in an antigen-specific manner when cells were restimulated with the fed antigen. When those cells were cultured and restimulated in vitro with the B-chain of insulin, we also observed a decrease in IFN-gamma expression and an increase in IL-4, TGF-beta and IL-10 expression. These results demonstrate that an orally protective epitope resides in the B-chain of insulin and that refeeding following adoptive transfer enhances protection. Finally, the orally administered antigen is associated with a decrease in Th1 responses and an increase in Th2 responses to the insulin B-chain.

Keywords: *Cytokines/IMMUNOLOGY *Diabetes Mellitus, Insulin-Dependent/IMMUNOLOGY *Diabetes Mellitus, Insulin-Dependent/PREVENTION & CONTROL *Insulin/ADMINISTRATION & DOSAGE *Insulin/IMMUNOLOGY *Th1 Cells/IMMUNOLOGY *Th2 Cells/IMMUNOLOGY
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M9811099

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