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T Cell‐Mediated Cytotoxicity via Fas/Fas Ligand Signaling in Helicobacter pylori ‐Infected Gastric Corpus
Author(s) -
Ishihara Shunji,
Fukuda Ryo,
Kawashima Kousaku,
Moriyama Nobuyuki,
Suetsugu Hiroshi,
Ishimura Norihisa,
Kazumori Hideaki,
Kaji Takekazu,
Sato Hiroshi,
Okuyama Toshihiko,
Rumi Karim M. A.,
Adachi Kyoichi,
Watanabe Makoto,
Kinoshita Yoshikazu
Publication year - 2001
Publication title -
helicobacter
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.206
H-Index - 79
eISSN - 1523-5378
pISSN - 1083-4389
DOI - 10.1046/j.1523-5378.2001.00043.x
Subject(s) - fas ligand , cytotoxic t cell , apoptosis , flow cytometry , cd8 , helicobacter pylori , biology , antigen , t cell , immune system , microbiology and biotechnology , immunology , in vitro , programmed cell death , biochemistry , genetics
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. Materials and 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‐γ (IFN‐γ). 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‐γ 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.