Open AccessHelicobacter pyloriModulates Lymphoepithelial Cell Interactions Leading to Epithelial Cell Damage through Fas/Fas Ligand Interactions
Author(s) -
Jide Wang,
Xuejun Fan,
Catharina Lindholm,
Michael Bennett,
Joe O'Connoll,
Fergus Shanahan,
Edward G. Brooks,
Victor E. Reyes,
Peter B. Ernst
Publication year - 2000
Publication title -
infection and immunity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.508
H-Index - 220
eISSN - 1070-6313
pISSN - 0019-9567
DOI - 10.1128/iai.68.7.4303-4311.2000
Subject(s) - fas ligand , biology , apoptosis , fas receptor , helicobacter pylori , cytotoxic t cell , cell culture , antibody , flow cytometry , enterochromaffin like cell , epithelium , gastric mucosa , cancer research , microbiology and biotechnology , immunology , programmed cell death , stomach , in vitro , biochemistry , genetics
Helicobacter pylori causes a common chronic infection of humans that leads to epithelial cell damage. Studies have shown that apoptosis of the gastric epithelium is increased during infection and this response is associated with an expansion of gastric T-helper type 1 (Th1) cells. We report that gastric T cells contribute to apoptosis of the epithelium by a Fas/Fas ligand (FasL) interaction. Fas receptor expression was detected on freshly isolated gastric epithelial cells by flow cytometry and immunohistochemistry, and this level of expression was increased during infection withH. pylori . The expression of Fas receptor on three gastric epithelial cell lines was increased byH. pylori , either alone or in combination with gamma interferon or tumor necrosis factor alpha. The role of Fas in apoptosis of gastric epithelial cell lines was evidenced by DNA fragmentation after cross-linking of Fas with specific antibodies. FasL expression was detected by immunohistochemistry on mononuclear cells in gastric biopsy specimens of infected but not uninfected subjects. Gastric T-cell lines were also shown to express FasL, as evidenced by reverse transcription-PCR and killing of target cells expressing Fas receptor. Moreover, these T-cell lines were capable of killing cultured gastric epithelial target cells and antibodies that block the interaction between Fas receptor and FasL inhibited this cytotoxic activity. These observations demonstrate that local Th1 cells may contribute to the pathogenesis of gastric disease duringH. pylori infection by increasing the expression of Fas on gastric epithelial cells and inducing apoptosis through Fas/FasL interactions.