HYPERSENSITIVITY IN THE SMALL INTESTINAL-MUCOSA .5. INDUCTION OF CELL-MEDIATED-IMMUNITY TO A DIETARY ANTIGEN

Abstract

Protein antigen feeding to adult mice results in reduced humoral and cell-mediated immune (CMI) responses when that antigen is subsequently presented, and also causes suppressor cell activation in the gut-associated lymphoid tissues (GALT). Abrogation of this tolerance to fed antigen was attempted by pretreating mice with 100 mg/kg cyclophosphamide [CPP] before oral immunization and challenge with ovalbumin [OA]. CPP-pretreated mice did not develop serum hemagglutinating antibodies, nor systemic CMI (as assessed by skin testing) after OA feeding. Evidence that CMI was induced in the GALT was provided by the significant inhibition of mesenteric lymph node cell migration from CPP-pretreated animals, but not from other control groups, in the presence of OA. Work on CMI reactions in the small intestine showed that the cell production rate in the crypts of Lieberkuhn and the intraepithelial lymphocyte count are reliable, although indirect, measures of mucosal CMI. CPP-pretreated, OA-immunized animals, which were fed 0.1 mg OA daily for 10 days before killing, had increased crypt cell mitoses and increased intraepithelial lymphocyte counts, indicating the presence of mucosal CMI response to OA. Mechanisms whereby CPP pretreatment leads to abrogation of tolerance and mucosal CMI induction are discussed.