T-cell responses to orally administered antigens. Study of the kinetics of lymphokine production after single and multiple feeding.
Mice fed a protein antigen develop a phenomenon called oral tolerance which is defined classically by the inability to respond to a parenteral challenge with the same antigen. In a recent report we showed that antigen-reactive T cells are not depleted following the development of oral tolerance to the soluble antigen ovalbumin (OVA). Instead mice remain highly sensitized so OVA-reactive T cells can be detected in the mesenteric lymph nodes (MLN), Peyer's patches and spleen. In the present study we show that OVA-specific T cells become sensitized in the MLN within 24 hr of feeding and that lymphokine responses peak 48-96 hr after feeding. T cells produced large amounts of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) but no interleukin-2 (IL-2) following activation in vitro. Responsiveness as measured by GM-CSF declined by days 8-11 while the ability to stimulate IFN-gamma secretion was more persistent. It was found in experiments with repeated feeding, 1 week apart, that the T-cell responsiveness was restimulated after each feed and that the magnitude and duration of the IFN-gamma or GM-CSF responses were almost identical to primary, even after 10 feeds.
Hoyne
G F
GF
Division of Molecular Biology, Institute for Child Health Research, Perth, Western Australia.
Thomas
W R
WR
D000818:Animals; D002478:Cells, Cultured; D004435:Eating / Q000276:immunology*; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000096:biosynthesis; D007108:Immune Tolerance; D007114:Immunization; D007371:Interferon-gamma / Q000096:biosynthesis; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis*; D008643:Mesentery; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage* / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*
D008222:Lymphokines; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D010047:Ovalbumin