DEFECTIVE GUT PROCESSING OF GLIADIN IN MICE WITH GRAFT-VERSUS-HOST ENTEROPATHY

The gut mucosa plays an important role in the induction of oral tolera nce. Extending previous observations, we have here shown that serum co ntaining gut-absorbed gliadin induces suppression of the specific syst emic immune response in recipient mice parenterally immunized with gli adin. Graft-versus-host reaction (GVHR) has profound effects on the gu t mucosa, representing a model of immune-mediated enteropathy. The aim of our work was to investigate the gut handling and processing of gli adin in mice with GvHR. Binding to enterocytes, passage through the ep ithelium, and ability of the epithelium to convert this antigen into a tolerogenic form were assessed in BDF1 mice weaned on gluten-free die t, 2 weeks after the induction of a semiallogeneic GVHR. Binding of gl iadin peptide B3144 to enterocytes was similar in controls and GVHR mi ce. After feed, serum levels of gliadin were comparable in the two gro ups of mice, but when serum collected from GvHR mice and containing gu t-absorbed gliadin was transferred intraperitoneally into naive recipi ent mice? this did not induce suppression of the specific immune respo nse. These experiments indicate that during GVHR enteropathy the abili ty of the intestine to convert gliadin into a tolerogenic form is lost . Defective antigen gut processing may contribute to the observed fail ure in oral tolerance induction.