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 parenter al 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 r emain highly sensitized so OVA-reactive T cells can be detected in the mesenteric lymph nodes (MLN), Peyer's patches and spleen. In the pres ent study we show that OVA-specific T cells become sensitized in the M LN within 24 hr of feeding and that lymphokine responses peak 48-96hr after feeding. T cells produced large amounts of granulocyte-macrophag e colony-stimulating factor (GM-CSF) and interferon-gamma (IFN-gamma) but no interleukin-2 (IL-2) following activation in vitro. Responsiven ess as measured by GM-CSF declined by days 8-11 while the ability to s timulate IFN-gamma secretion was more persistent. It was found in expe riments with repeated feeding, 1 week apart, that the T-cell responsiv eness was restimulated after each feed and that the magnitude and dura tion of the IFN-gamma or GM-CSF responses were almost identical to pri mary, even after 10 feeds.