MAJOR HISTOCOMPATIBILITY ANTIGEN-RESTRICTED CYTOTOXICITY IN INFLAMMATORY BOWEL-DISEASE

Background: The role of cytotoxicity mediated by peripheral blood mononuclear cells for colonic epithelial cells in inflammatory bowel disease (IBD) is still controversial. To clarify it, we studied major histocompatibility antigen (MHC)-restricted T cell-mediated cytotoxicity (CTL). Methods: Cytotoxicity was measured by 51Cr release from colonic cells after the 6-hour incubation with peripheral blood mononuclear cells in 11 IBD patients (6 with Crohn's disease and 5 with ulcerative colitis). Results: CTL activity ( E T ratio = 200:1 or 100:1) for autologous target cells was significantly increased (22%-40%) in 5 of 6 CD and 4 of 5 UC patients (22%-64%) compared with that for allogeneic target cells. The increase in CTL activity was mainly inhibited by anti-MHC class I and CD8 monoclonal antibodies (50 μg/mL), while it was partially inhibited by anti-MHC class II or CD4 antibodies in some patients. Complement-mediated depletion of CD2+ cells also significantly decreased CTL activity. Conclusions: The results indicate that MHC-restricted T cell cytotoxicity may play a role in mucosal damage in some patients of IBD. © 1993.