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. doi: 10.1006/jaut.1997.0148.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Administration, Oral
  • Adoptive Transfer
  • Animals
  • Autoimmunity
  • Cytokines / immunology*
  • Diabetes Mellitus, Type 1 / immunology*
  • Diabetes Mellitus, Type 1 / prevention & control*
  • Disease Models, Animal
  • Female
  • Immunodominant Epitopes / administration & dosage
  • Immunodominant Epitopes / chemistry
  • Immunosuppression
  • In Vitro Techniques
  • Insulin / administration & dosage*
  • Insulin / chemistry
  • Insulin / immunology*
  • Lymphocyte Activation
  • Male
  • Mice
  • Mice, Inbred NOD
  • Ovalbumin / immunology
  • Th1 Cells / immunology*
  • Th2 Cells / immunology*

Substances

  • Cytokines
  • Immunodominant Epitopes
  • Insulin
  • Ovalbumin