Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation
✍ Scribed by Jenkins, David; Seth, Rashmi; Kummer, J. Alain; Scott, Brian B.; Hawkey, Christopher J.; Robins, R. Adrian
- Publisher
- John Wiley and Sons
- Year
- 2000
- Tongue
- English
- Weight
- 220 KB
- Volume
- 190
- Category
- Article
- ISSN
- 0022-3417
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✦ Synopsis
The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may re¯ect disordered humoral or cell-mediated effector mechanisms, respectively. Mucosal biopsies from untreated in¯ammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule speci®cally associated with cell-mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcriptionpolymerase chain reaction and enzyme-linked oligonucleotide chemiluminescence assay. Mucosal biopsies were analysed by immunohistochemistry for granzyme B protein and lymphocyte markers and for the presence of apoptotic cells by terminal deoxynucleotidyl transferase end labelling. Granzyme B mRNA was elevated in Crohn's disease, but not in ulcerative colitis or control mucosal biopsies. Granzyme B mRNA levels correlated with interferon gamma mRNA levels in Crohn's disease. Granzyme B was expressed in CD3+, CD8+ T cells in the lamina propria of Crohn's disease mucosa and there were signi®cantly more apoptotic cells in the lamina propria in Crohn's disease. In conclusion, granzyme B-expressing T lymphocytes are present in the focal mucosal lesions of Crohn's disease, together with spatially related apoptotic cell death. These results support the hypothesis that T-cell-mediated cytotoxic effector mechanisms may play a role in Crohn's disease.