Apoptotic depletion of infiltrating mucosal lymphocytes associated with Fas ligand expression by Helicobacter pylori-infected gastric mucosal epithelium: human glandular stomach as a site of immune privilege.
H. pylori infection almost invariably results in chronic gastritis, but only a proportion of patients develops severe destruction of epithelial glandular structure or peptic ulcer. To confirm the recent data obtained in testis and eye, showing that Fas ligand is involved in the phenomenon of "immune privilege," expression of Fas receptor and its ligand of the stomach was investigated in a panel of gastric biopsies obtained from patients H. pylori-positive (N = 42) and with H. pylori-negative (N = 18) by two-color flow cytometry. The results show that membrane-bound Fas ligand protein is constitutively expressed on freshly isolated human gastric mucosal epithelium coupled with infiltrating lymphocytes. There was significant overexpression of Fas receptor and its ligand, and a higher frequency of apoptotic cell death detected by TUNEL in epithelium and infiltrating lymphocytes in H. pylori-infected patients. These findings suggest that involvement of Fas receptor and its ligand system contributes to some extent to mucosal damage in H. pylori-associated gastritis. However, the more specific findings are apoptotic depletion of invading mucosal lymphocytes associated with Fas ligand expression by gastric epithelium. These provide the first direct quantitative evidence to support Fas receptor counterattack and/or paracrine fratricide as a mechanism of immune privilege in vivo in the H. pylori-infected glandular stomach.
Koyama
S
S
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba-City, Ibaraki, Japan.
D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D000954:Antigens, Surface / Q000276:immunology; D017209:Apoptosis; D004848:Epithelium / Q000276:immunology / Q000382:microbiology; D053222:Fas Ligand Protein; D005260:Female; D005434:Flow Cytometry; D005753:Gastric Mucosa / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D005756:Gastritis / Q000276:immunology* / Q000382:microbiology*; D015964:Gene Expression Regulation, Bacterial; D016481:Helicobacter Infections / Q000276:immunology* / Q000382:microbiology* / Q000473:pathology; D016480:Helicobacter pylori; D006801:Humans; D020287:In Situ Nick-End Labeling; D008214:Lymphocytes / Q000276:immunology*; D008297:Male; D008562:Membrane Glycoproteins / Q000276:immunology*; D008875:Middle Aged; D015854:Up-Regulation; D019014:fas Receptor / Q000276:immunology*
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor