Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation

J Pathol. 2000 Feb;190(2):184-9. doi: 10.1002/(SICI)1096-9896(200002)190:2<184::AID-PATH531>3.0.CO;2-E.


The mechanisms of tissue damage in ulcerative colitis and Crohn's disease may reflect disordered humoral or cell-mediated effector mechanisms, respectively. Mucosal biopsies from untreated inflammatory bowel disease patients and normal controls were analysed for the expression of granzyme B, a cytotoxic effector molecule specifically associated with cell-mediated immunity, and for regulatory cytokines. Messenger RNA (mRNA) was analysed by reverse transcription-polymerase 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 significantly 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Apoptosis*
  • Child
  • Colitis, Ulcerative / enzymology
  • Colitis, Ulcerative / immunology*
  • Colitis, Ulcerative / pathology
  • Crohn Disease / enzymology
  • Crohn Disease / immunology*
  • Crohn Disease / pathology
  • Cytokines / genetics
  • Cytokines / metabolism*
  • Female
  • Gene Expression
  • Granzymes
  • Humans
  • Leukocytes, Mononuclear / immunology
  • Male
  • Middle Aged
  • RNA, Messenger / genetics
  • Serine Endopeptidases / genetics
  • Serine Endopeptidases / metabolism*
  • T-Lymphocytes, Cytotoxic / immunology


  • Cytokines
  • RNA, Messenger
  • GZMB protein, human
  • Granzymes
  • Serine Endopeptidases