Expression of HLA-DR antigens in inflammatory bowel disease mucosa: Role of intestinal lamina propria mononuclear cell-derived interferon ?

Abstract

The expression of HLA-DR antigens on the surface of immune cells is crucial for appropriate antigen presentation and a normal immune response. In the intestinal mucosa involved by Crohn's disease and ulcerative colitis the expression of HLA-DR antigens is increased in both immune and nonimmune cells, a phenomenon probably mediated by soluble factors, such as interferon γ, produced by locally activated mononuclear cells. This study investigated the production of interferon γ by inflammatory bowel disease and control intestinal lamina propria mononuclear cells, and the ability of this endogenously produced lymphokine to induce expression of HLA-DR antigens on the monocytic cell lines U937 and ML3. After in vitro stimulation with interleukin 2 or phytohemagglutinin, but not spontaneously, lamina propria mononuclear cells produced variable amounts of interferon γ, and their culture supernatants could induce de novoexpression of HLA-DR antigens on the monocytic indicator cells. When the mononuclear cells were derived from inflammatory bowel disease mucosa, both the amount of interferon γ present in the supernatants and the number of HLA-DR-positive cells induced by these supernatants were decreased as compared to controls. These results suggest that, in inflammatory bowel disease, interferon γ may not be the only mediator of HLA-DR induction in the gut and that other soluble factors or agents, alone or interacting with interferon γ, may also be responsible for this event, resulting in the enhanced HLA-DR antigen expression observed in the inflamed intestinal mucosa.