The role of activated cytotoxic T cells in inflammatory bowel disease

The role of cell-mediated cytotoxicity in the pathogenesis of ulcerative co litis and Crohn's disease has been controversial since reports indicating e ither a decreased, or an increased, activity of cytotoxic T cells in active stages of inflammatory bowel disease exist. Some of these discrepancies ma y be attributed to the fact that so far mostly peripheral blood lymphocytes rather than intestinal T cells have been examined. To overcome some of the se limitations we performed in situ hybridizations for the detection of per forin and granzyme A mRNA expressing cells, i.e. of cytotoxic cells activat ed in situ, in the affected intestinal mucosa. These studies revealed incre ased frequencies of activated, cytotoxic T cells in active stages of ulcera tive colitis and Crohn's disease. Interestingly, activated perforin mRNA ex pressing T cells are present both in the CD4 and in the CD8 T cell subsets. In the latter T cell subset up to 60% of the mucosal T cells isolated from the affected sites express perforin mRNA at detectable levels. The elevate d frequency of activated cytotoxic cells and their histological distributio n also in close proximity to the epithelial cells may thus indicate an impo rtant role for cytotoxic cells in the pathogenesis of inflammatory bowel di sease since activated cytotoxic T cells may further exacerbate the inflamma tory process through the production of pro-inflammatory cytokines such as i nterferon-gamma or tumor necrosis factor-alpha, but also through the releas e of pre-inflammatory cytokines and chemokines upon lysis of epithelial cel ls and the increased influx of luminal antigens at the site of epithelial e rosions.