ACTIVATED CD4(-CELLS ARE PRESENT IN INCREASED NUMBERS IN THE INTESTINAL-MUCOSA FROM PATIENTS WITH ACTIVE INFLAMMATORY BOWEL-DISEASE() AND CD8(+) CYTOTOXIC)

The contribution of cell-medial:ed cytotoxicity to the pathogenesis of inflammatory bowel disease (IBD) is controversial, and results of in vitro assays vary according to experimental procedures. Therefore, we compared the frequency of cytotoxic effector cells in situ. On tissue sections of controls (n = 11), low frequencies of granzyme A and perfo rin mRNA-expressing cells are found in the lamina propria (1.77 +/- 0. 15% and 1.46 +/- 0.12%, respectively) and in the epithelial cell layer (0.76 +/- 0.12% and 0.66 +/- 0.10%, respectively). In patients with I BD (n = 33), corresponding values were significantly (P < 0.02) higher , 6.1 +/- 0.40% and 5.92 +/- 0.57% for granzyme A and perforin express ion in the lamina propria and 2.50 +/- 0.19% and 2.59 +/- 0.28%, respe ctively, in the epithelial compartment. Differences between ulcerative colitis and Crohn's disease are statistically not significant (P > 0. 33), Activated cytotoxic cells are preferentially found at sites facin g the intestinal lumen. Perforin mRNA-expressing cells are mainly CD8 T cells. CD4+ T cells expressing perforin mRNA are mainly isolated fr om affected areas of patients with Crohn's disease. Immunostaining for perforin protein generally coincides with perforin mRNA in situ. Thes e data demonstrate that cytotoxic cells are vigorously activated in si tu in the intestinal mucosa of patients with active IBD.