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 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-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 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-beta 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-gamma. These results demonstrate that orally administered insulin can induce regulatory T-cells secreting IL-4, IL-10, and TGF-beta and that Th2 responses to oral insulin could be augmented in a synergistic way by feeding SEA and insulin B-chain together.
Maron
R
R
Center for Neurologic Diseases, Brigham and Women's Hospital, Boston, Massachusetts, USA.
Palanivel
V
V
Weiner
H L
HL
Harn
D A
DA
D000284:Administration, Oral; D000818:Animals; D000947:Antigens, Helminth / Q000008:administration & dosage*; D004306:Dose-Response Relationship, Immunologic; D007328:Insulin / Q000276:immunology*; D016753:Interleukin-10 / Q000096:biosynthesis*; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D051379:Mice; D016688:Mice, Inbred NOD / Q000276:immunology*; D009844:Oligosaccharides / Q000276:immunology; D012550:Schistosoma mansoni / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*
D000947:Antigens, Helminth; D007328:Insulin; D009844:Oligosaccharides; D016212:Transforming Growth Factor beta; D016753:Interleukin-10