Dual mechanisms of inhibition of the immune response by enterocytes isolated from the rat small intestine

Abstract

Summary Antigen presentation by enterocytes isolated from the rat small bowel was studied by using T cell proliferation, and immunorcgulatory function in an antigen-driven culture system, as indicator systems. Lymph node T cells obtained from rats immunized with ovalbumin (OA) failed to divide when cultured for 4 days in the presence of freshly isolated la+ enterocytes and OA. However, cell division was noted when enterocytes were removed after 18 h by Percoll gradient centrifugation, followed by culture ofT cells for a further 4 days in the absence of antigen. The failure to divide in the primary culture was due to the secretion by enterocytes ofa dialysable non-specific inhibitor. Antigen presentation by enterocytes was specific and was inhibited by monoclonal mouse anti-rat la antibody, 0X6. An epithelial cell line (REC-2) was established from normal rat small intestine. These cells expressed la molecules following incubation with Concanavalin-A stimulated spleen cell supernatant, and were capable of both presenting antigen, and inducing interieukin-2 (lL-2) production, when cultured with primed T cells. Furthermore. la' REC-2 cells functioned as stimulators in a primary mixed lymphocyte reaction (MLR). Both OA-primed T cells activated by enterocytes and antigen, and allogeneic MLR-activated T cells, mediated suppression which was not specific for the initiating antigen. These experiments indicated two mechanisms mediate suppression of cell division in gut mucosa. The contribution of these mechanisms to the control of inflammation at mucosal sites requires investigation.