Oral Administration of Schistosome Egg Antigens and Insulin B-Chain Generates and Enhances Th2-Type Responses in NOD Mice

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In murineSchistosoma mansoni,parenteral administration of parasite eggs or saline-soluble egg antigens (SEA), generates Th2 T-cell responses to both schistosome-specific and unrelated third-party antigens. Oral administration of insulin to NOD mice suppresses or delays the onset of diabetes by skewing the response toward CD4+Th2 cells and TGF-β producing cells. From these two independent sets of observations, we initiated the present study to determine if oral administration of SEA would stimulate Th2-type cytokine responses when mice were fed SEA alone or in tandem with insulin B-chain. Our results show that feeding NOD mice with either insulin B-chain or SEA alone significantly inhibits proliferation to the immunizing antigen. When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-β production. Furthermore, feeding SEA in combination with insulin B-chain augmented the level of IL-10 production to insulin. T-cell lines established from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytokines whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-γ. These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-β and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together.