T-cell lymphokine response to orally administered proteins during priming and unresponsiveness

Feeding antigens induces an immunological unresponsiveness termed oral tolerance but under some conditions, for example following the administration of cyclophosphamide (CY), immunity can be induced. These observations have usually been made by studying antibody production and delayed hypersensitivity with little attention given to other measurements of cellular activation. We have therefore examined the lymphokines produced by T cells obtained after the induction of oral tolerance or intragastric priming. Cells isolated from the spleen and Peyer's patches (PP) of tolerized mice could secrete high levels of interferon-gamma (IFN-gamma) and moderate levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) in response to antigen while interleukin-2 (IL-2), IL-3 and IL-4 could not be detected. Mesenteric lymph node (MLN) cells of tolerized mice did not respond to antigen unless spleen adherent cells were added to the cultures where IFN-gamma and GM-CSF were produced. Intragastric priming was achieved by feeding antigen to CY-treated mice. T cells from the spleen, MLN and PP of these mice could produce GM-CSF, IFN-gamma, some IL-3 but little or no IL-2 and IL-4. The ability of MLN cells to proliferate with antigen in vitro was low and corresponded to low IL-2 production. Thus T cells from fed mice secrete a defined pattern of lymphokines which differs in tolerizing and priming regimes.