Activated CD4+ and CD8+ cytotoxic cells are present in increased numbers in the intestinal mucosa from patients with active inflammatory bowel disease

Am J Pathol. 1998 Jan;152(1):261-8.


The contribution of cell-mediated 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 perforin 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 IBD (n = 33), corresponding values were significantly (P < 0.02) higher, 6.1 +/- 0.40% and 5.92 +/- 0.57% for granzyme A and perforin expression in the lamina propria and 2.50 +/- 0.19% and 2.59 +/- 0.28%, respectively, 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 facing the intestinal lumen. Perforin mRNA-expressing cells are mainly CD8+ T cells. CD4+ T cells expressing perforin mRNA are mainly isolated from affected areas of patients with Crohn's disease. Immunostaining for perforin protein generally coincides with perforin mRNA in situ. These data demonstrate that cytotoxic cells are vigorously activated in situ in the intestinal mucosa of patients with active IBD.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • CD4-Positive T-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / physiology*
  • CD8-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / physiology*
  • Female
  • Humans
  • Inflammatory Bowel Diseases / metabolism
  • Inflammatory Bowel Diseases / pathology*
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Leukocyte Count
  • Lymphocyte Activation / physiology*
  • Male
  • Membrane Glycoproteins / metabolism
  • Perforin
  • Pore Forming Cytotoxic Proteins
  • T-Lymphocytes, Cytotoxic / pathology*


  • Membrane Glycoproteins
  • Pore Forming Cytotoxic Proteins
  • Perforin