title: Expression of the programmed death ligand 1, B7-H1, on gastric epithelial cells after Helicobacter pylori exposure promotes development of CD4+ CD25+ FoxP3+ regulatory T cells.
abstract: During Helicobacter pylori infection, T cells are recruited to the gastric mucosa, but the host T-cell response is not sufficient to clear the infection. Some of the recruited T cells respond in a polarized manner to a Th1 response, while others become anergic. We have previously shown that T-cell anergy may be induced during infection by the interaction of T cells with B7-H1, which is up-regulated on the gastric epithelium during H. pylori infection. Recently, regulatory T (Treg) cells with a CD4(+) CD25(high) FoxP3(+) phenotype were found at an increased frequency in the gastric mucosa of biopsy specimens from H. pylori-infected patients. While Treg cells are important in maintaining tolerance, they can also suppress immune responses during infection. In this study, we examined the induction of the Treg phenotype when naïve T cells were incubated with gastric epithelial cells exposed to H. pylori. The frequency of this phenotype was markedly decreased when B7-H1 was blocked with monoclonal antibodies or its expression was blocked with small interfering RNA. The functional role of these Treg cells was assessed in proliferation assays when the cells were cocultured with activated T cells, which effectively decreased proliferation of the cells.
authors.affiliation: Departmen tof Pediatrics, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555, USA.
authors.forename: Ellen J
authors.initials: EJ
authors.lastname: Beswick
authors.forename: Irina V
authors.initials: IV
authors.lastname: Pinchuk
authors.forename: Soumita
authors.initials: S
authors.lastname: Das
authors.forename: Don W
authors.initials: DW
authors.lastname: Powell
authors.forename: Victor E
authors.initials: VE
authors.lastname: Reyes
mesh_terms: D000328:Adult; D015703:Antigens, CD / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D060890:B7-H1 Antigen; D002454:Cell Differentiation / Q000276:immunology*; D002460:Cell Line; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D015536:Down-Regulation / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000096:biosynthesis*; D005753:Gastric Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D016130:Immunophenotyping; D016753:Interleukin-10 / Q000096:biosynthesis / Q000235:genetics; D008213:Lymphocyte Activation / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis / Q000235:genetics; D015854:Up-Regulation / Q000276:immunology
chemical_list: D015703:Antigens, CD; D060890:B7-H1 Antigen; C423236:CD274 protein, human; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D016212:Transforming Growth Factor beta; D016753:Interleukin-10