ArticleProceedings of the National Academy of Sciences of the United States of America2004
Inhibition of primary human T cell proliferation by Helicobacter pylori vacuolating toxin (VacA) is independent of VacA effects on IL-2 secretion.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 113 papers.
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Who cites it
113 citing papers in PubMed, 260 citations in OpenAlex.
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- Cultivation and molecular characterization of viable Helicobacter pylori from the root canal of 170 deciduous teeth of children.Cell communication and signaling : CCS · 2024Article
- Developing a potent vaccine againstExpert reviews in molecular medicine · 2024Review
- Structural Analysis of Membrane-associated Forms of Helicobacter pylori VacA Toxin.Journal of molecular biology · 2024Article
- The Most Recent Insights into the Roots of Gastric Cancer.Life (Basel, Switzerland) · 2024Review
- The immunopathogenesis ofFrontiers in microbiology · 2024Review
- Mycoplasma genitalium Protein of Adhesion Suppresses T Cell Activation via CypA-CaN-NFAT Pathway.Microbiology spectrum · 2023Article
- Outer Membrane Vesicles (OMVs) as Biomedical Tools and Their Relevance as Immune-Modulating Agents againstInternational journal of molecular sciences · 2023Review
- The role of gastric microecological dysbiosis in gastric carcinogenesis.Frontiers in microbiology · 2023Review
- Article
- Helicobacter pylori Infection, Its Laboratory Diagnosis, and Antimicrobial Resistance: a Perspective of Clinical Relevance.Clinical microbiology reviews · 2022Review
- The Effects of Vitamins and Micronutrients onJournal of immunology research · 2022Review
- Specific cannabinoids revive adaptive immunity by reversing immune evasion mechanisms in metastatic tumours.Frontiers in immunology · 2022Article
- Lymphostatin, a virulence factor of attaching and effacingFrontiers in cellular and infection microbiology · 2022Article
- The Efficacy of Cancer Immunotherapies Is Compromised byFrontiers in immunology · 2022Review
- Interplay and cooperation of Helicobacter pylori and gut microbiota in gastric carcinogenesis.BMC microbiology · 2021Review
- Review
53 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Recent evidence indicates that the secreted Helicobacter pylori vacuolating toxin (VacA) inhibits the activation of T cells. VacA blocks IL-2 secretion in transformed T cell lines by suppressing the activation of nuclear factor of activated T cells (NFAT). In this study, we investigated the effects of VacA on primary human CD4(+) T cells. VacA inhibited the proliferation of primary human T cells activated through the T cell receptor (TCR) and CD28. VacA-treated Jurkat T cells secreted markedly diminished levels of IL-2 compared with untreated cells, whereas VacA-treated primary human T cells continued to secrete high levels of IL-2. Further experiments indicated that the VacA-induced inhibition of primary human T cell proliferation was not attributable to VacA effects on NFAT activation or IL-2 secretion. We show here that VacA suppresses IL-2-induced cell-cycle progression and proliferation of primary human T cells without affecting IL-2-dependent survival. Through the analysis of a panel of mutant VacA proteins, we demonstrate that VacA-mediated inhibition of T cell proliferation requires an intact N-terminal hydrophobic region necessary for the formation of anion-selective membrane channels. Remarkably, we demonstrate that one of these mutant VacA proteins [VacA-Delta(6-27)] abrogates the immunosuppressive actions of wild-type VacA in a dominant-negative fashion. We suggest that VacA may inhibit the clonal expansion of T cells that have already been activated by H. pylori antigens, thereby allowing H. pylori to evade the adaptive immune response and establish chronic infection.
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