Differential levels of granzyme B, regulatory cytokines, and apoptosis in Crohn's disease and ulcerative colitis at first presentation.
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.
Jenkins
D
D
Department of Clinical Laboratory Sciences, University Hospital, Nottingham, UK.
Seth
R
R
Kummer
J A
JA
Scott
B B
BB
Hawkey
C J
CJ
Robins
R A
RA
D000293:Adolescent; D000328:Adult; D000368:Aged; D017209:Apoptosis; D002648:Child; D003093:Colitis, Ulcerative / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D003424:Crohn Disease / Q000201:enzymology / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015870:Gene Expression; D053804:Granzymes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D012697:Serine Endopeptidases / Q000235:genetics / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D016207:Cytokines; D012333:RNA, Messenger; C509213:GZMB protein, human; D053804:Granzymes; D012697:Serine Endopeptidases