T cell-mediated cytotoxicity via Fas/Fas ligand signaling in Helicobacter pylori-infected gastric corpus.
BACKGROUND
Helicobacter pylori infection induces T helper-1 immune responses in inflamed mucosa. However, the role of T cell-mediated cytotoxicity in the induction of epithelial apoptosis is still unclear. The aim of this study was to investigate the involvement of the Fas/Fas ligand (Fas/Fas-L) system in the H. pylori-infected gastric corpus.


METHODS
Gastric fundic biopsy specimens were taken from patients with and without H. pylori infection. The expression of Fas and Fas-L was examined by immunohistochemistry and RT-PCR. Subsets of gastric infiltrating T cells in the biopsy specimens were studied by immunohistochemistry and flow cytometry. In histological sections, apoptosis was detected by the TUNEL method. We studied the in vitro expression of Fas-L in peripheral T cells after stimulation with H. pylori antigen and interferon-gamma (IFN-gamma). The Fas-mediated in vitro cytotoxicity of activated T cells was assessed by flow cytometry.


RESULTS
The numbers of CD4+ and CD8+ T cells were greater in H. pylori-infected subjects. Fas expression was abundantly increased on fundic gland epithelium, and Fas-L was detected on lamina propria mononuclear cells in H. pylori-infected mucosa. TUNEL-positive epithelial cells were also increased in H. pylori-infected subjects. H. pylori antigen and IFN-gamma induced Fas-L mRNA expression in both CD4+ and CD8+ T cells. In cytotoxic assay, activated T cells induced apoptosis in AGS cells, which could be significantly inhibited by neutralizing Fas-L antibody.


CONCLUSIONS
T cell-mediated cytotoxicity via Fas/Fas-L signaling may contribute to the induction of apoptosis in gastric epithelial cells during H. pylori infection.
Ishihara
S
S
Department of Internal Medicine II, Shimane Medical University, Izumo, Shimane, Japan. si360405@shimane-med.ac.jp
Fukuda
R
R
Kawashima
K
K
Moriyama
N
N
Suetsugu
H
H
Ishimura
N
N
Kazumori
H
H
Kaji
T
T
Sato
H
H
Okuyama
T
T
Rumi
K M
KM
Adachi
K
K
Watanabe
M
M
Kinoshita
Y
Y
D000328:Adult; D000368:Aged; D017209:Apoptosis; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D004847:Epithelial Cells; D053222:Fas Ligand Protein; D005260:Female; D005753:Gastric Mucosa / Q000276:immunology* / Q000473:pathology; D016481:Helicobacter Infections / Q000276:immunology*; D016480:Helicobacter pylori / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism*; D008875:Middle Aged; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000276:immunology*; D019014:fas Receptor / Q000378:metabolism*
C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D019014:fas Receptor