Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype

doi:10.1016/S0016-5085(98)70531-1

Gastroenterology

Volume 114, Issue 3, March 1998, Pages 482-492

https://doi.org/10.1016/S0016-5085(98)70531-1 Get rights and content

Abstract

Background & Aims: Studies have shown that gastric T cells are increased during Helicobacter pylori infection. The purpose of this study was to characterize the human gastric T-cell responses in the presence or absence of H. pylori. Methods: T-cell surface antigens were examined by immunohistochemistry or after isolation for evaluation of surface antigens and cytoplasmic cytokines using flow cytometry. Results: CD4⁺ and CD8⁺ T cells were increased in situ during infection with H. pylori. Freshly isolated gastric T cells expressed cytoplasmic interferon gamma (IFN-γ) and interleukin (IL)-2 after a brief stimulation. Simultaneous four-color flow cytometry demonstrated that both CD8⁺ and CD4⁺ T cells expressed IFN-γ. Because stimulation through CD30 favors the induction of IL-5 and Th2 cells, gastric and colonic T cells were examined for CD30 expression. Consistent with the notion that Th2 cells are found in the intestine, CD30 was evident throughout the lamina propria of the colon but was virtually absent in the stomach. Furthermore, freshly isolated gastric T cells produced little IL-4 and virtually no IL-5 or tumor necrosis factor β. Conclusions: These observations show that gastric T cells resemble the Th1 type, which may explain their failure to induce immunity to H. pylori and their ability to contribute to the pathogenesis of gastric disease.

GASTROENTEROLOGY 1998;114:482-492

Section snippets

Subject population

Biopsy specimens of the gastric antrum were obtained from consenting subjects aged 20–55 years undergoing gastroesophageal duodenoscopy for various clinical indications as approved by our respective institutional review boards at Baylor College of Medicine and the University of Texas Medical Branch. Individuals regularly using nonsteroidal anti-inflammatory drugs or antisecretory drugs were excluded from the donor population. Subjects were considered infected if H. pylori was detected either by

Characterization of gastric T cells in situ and after isolation

To ensure that preparations of isolated gastric T cells were generally representative of the T-cell population in situ, immunohistochemistry for CD3, CD4, and CD8 was performed on frozen sections of antral biopsy specimens obtained from infected and uninfected individuals. Whereas staining with the isotype control did not mark any cells, specific antibodies showed that infection with H. pylori is associated with a marked T-cell infiltrate in the epithelium as well as in the lamina propria

Discussion

Previous studies have examined the ability of H. pylori to stimulate IFN-γ production and have described the presence of IFN-γ–producing cells in gastric tissue.26, 27, 28 However, the IFN-γ–producing cells obtained immediately after isolation from the gastric mucosa have not been characterized in detail. The data in this report support the hypothesis that the gastric T-cell population resembles the Th1 subset of helper T cells. Moreover, these cells are relatively restricted in their cytokine

Acknowledgements

The authors thank the endoscopy staff at the University of Texas Medical Branch and the Veterans Administration Hospital in Houston for their help in collecting the biopsy specimens. The technical assistance of Jennifer Graham and the staff in the histology service of the Department of Pathology at the University of Texas Medical Branch is also appreciated. Mark Griffin provided assistance in the development of the four-color flow-cytometric analysis and the evaluation of the data.

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^☆: Address requests for reprints to: Peter B. Ernst, Children's Hospital, University of Texas Medical Branch, 301 University Boulevard, Galveston, Texas 77555-0366. e-mail: [email protected]; fax: (409) 772-1761.

^☆☆: Supported by the John Sealy Memorial Endowment Fund for Biomedical Research and U.S. Public Health Service grants DK 50669, DK 51577, and CHD 35741.

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Alimentary TractLymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype☆,☆☆

Abstract

Section snippets

Subject population

Characterization of gastric T cells in situ and after isolation

Discussion

Acknowledgements

Gastroenterology

Gastroenterology

Lancet

Gastroenterology

Gastroenterology

Immunol Today

Immunol Today

Lancet

Molecular characterization of the 128-kDa immunodominant antigen of Helicobacter pylori associated with cytotoxicity and duodenal ulcer

Proc Natl Acad Sci USA

Infection with Helicobacter pylori strains possessing cagA is associated with an increased risk of developing adenocarcinoma of the stomach

Cancer Res

Helicobacter pylori induced interleukin-8 expression in gastric epithelial cells is associated with CagA positive phenotype

J Clin Pathol

Helicobacter pylori picB, a homologue of the Bordetella pertussis toxin secretion protein, is required for induction of IL-8 in gastric epithelial cells

Mol Microbiol

Heightened inflammatory response and cytokine expression in vivo to cagA+ Helicobacter pylori strains

Lab Invest

The immunopathogenesis of gastroduodenal disease associated with Helicobacter pylori infection

Curr Opin Gastroenterol

Human monoclonal antibodies from stomach carcinoma patients react with Helicobacter pylori and stimulate stomach cancer cells in vitro

Cancer

Idiotype identity in a MALT-type lymphoma and B cells in Helicobacter pylori associated chronic gastritis

Lab Invest

Antigastric autoantibodies in Helicobacter pylori gastritis: prevalence, in-situ binding sites and clues for clinical relevance

Virchows Arch

Potential role molecular mimicry between Helicobacter pylori lipopolysaccharide and host Lewis blood group antigens in autoimmunity

Infect Immun

Transforming growth factor B induces IgA production and acts additively with interleukin 5 for IgA production

J Exp Med

IL-6 is a potent cofactor of IL-1 in IgM synthesis and of IL-5 in IgA synthesis

J Immunol

Transforming growth factor-β1 is a costimulator for IgA production

J Immunol

IL-2 and a contact-mediated signal provided by TCRab+ or TCRgd+ CD4+ T cells induce polyclonal Ig production by committed human B cells: enhancement by IL-5, specific inhibition of IgA synthesis by IL-4

J Immunol

Oral immunization against Helicobacter pylori

Infect Immun

Recombinant antigens prepared from the urease subunits of Helicobacter spp.: evidence of protection in a mouse model of gastric infection

Infect Immun

Alimentary Tract
Lymphocytes in the human gastric mucosa during Helicobacter pylori have a T helper cell 1 phenotype☆,☆☆

Heightened inflammatory response and cytokine expression in vivo to cagA⁺ Helicobacter pylori strains

IL-2 and a contact-mediated signal provided by TCRab⁺ or TCRgd⁺ CD4⁺ T cells induce polyclonal Ig production by committed human B cells: enhancement by IL-5, specific inhibition of IgA synthesis by IL-4