ORAL-ADMINISTRATION OF SCHISTOSOME EGG ANTIGENS AND INSULIN B-CHAIN GENERATES AND ENHANCES TH2-TYPE RESPONSES IN NOD MICE

In murine Schistosoma mansoni, parenteral administration of parasite e ggs or saline-soluble egg antigens (SEA), generates Th2 T-cell respons es to both schistosome-specific and unrelated third-party antigens, Or al administration of insulin to NOD mice suppresses or delays the onse t of diabetes by skewing the response toward CD4(+) Th2 cells and TGF- beta 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 SE A alone or in tandem with insulin B-chain. Our results show that feedi ng NOD mice with either insulin B-chain or SEA alone significantly inh ibits proliferation to the immunizing antigen. When cytokine profiles were examined, feeding led to a predominance of IL-10 and TGF-beta pro duction. Furthermore, feeding SEA in combination with insulin B chain augmented the level of IL-10 production to insulin. T-cell Lines estab lished from SEA-fed and -immunized mice secreted IL-4 and IL-10 cytoki nes whereas the T-cell lines from control-fed mice immunized with SEA secreted predominantly IL-2 and IFN-gamma, These results demonstrate t hat orally administered insulin can induce regulatory T-cells secretin g IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin cou ld be augmented in a synergistic way by feeding SEA and insulin B-chai n together. (C) 1998 Academic Press.