title: Helicobacter pylori induces activation of human peripheral γδ+ T lymphocytes.
abstract: Helicobacter pylori is a gram-negative bacterium that causes gastric and duodenal diseases in humans. Despite a robust antibody and cellular immune response, H. pylori infection persists chronically. To understand if and how H. pylori could modulate T cell activation, in the present study we investigated in vitro the interaction between H. pylori and human T lymphocytes freshly isolated from peripheral blood of H. pylori-negative donors. A direct interaction of live, but not killed bacteria with purified CD3+ T lymphocytes was observed by microscopy and confirmed by flow cytometry. Live H. pylori activated CD3+ T lymphocytes and predominantly γδ+ T cells bearing the TCR chain Vδ2. Upon interaction with H. pylori, these cells up-regulated the activation molecule CD69 and produced cytokines (such as TNFα, IFNγ) and chemokines (such as MIP-1β, RANTES) in a non-antigen-specific manner. This activation required viable H. pylori and was not exhibited by other gram-negative bacteria. The cytotoxin-associated antigen-A (CagA), was at least partially responsible of this activation. Our results suggest that H. pylori can directly interact with T cells and modulate the response of γδ+ T cells, thereby favouring an inflammatory environment which can contribute to the chronic persistence of the bacteria and eventually to the gastric pathology.
authors.affiliation: Novartis Vaccines and Diagnostics Research Center, Siena, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Romi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Soldaini
authors.forename: Laura
authors.initials: L
authors.lastname: Pancotto
authors.forename: Flora
authors.initials: F
authors.lastname: Castellino
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Del Giudice
authors.forename: Francesca
authors.initials: F
authors.lastname: Schiavetti
mesh_terms: D017252:CD3 Complex / Q000378:metabolism*; D018920:Coculture Techniques; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D016481:Helicobacter Infections / Q000097:blood*; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008213:Lymphocyte Activation; D018613:Microscopy, Confocal / Q000379:methods; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D012307:Risk Factors; D013601:T-Lymphocytes / Q000378:metabolism* / Q000382:microbiology*
chemical_list: D017252:CD3 Complex; D011948:Receptors, Antigen, T-Cell; D016692:Receptors, Antigen, T-Cell, gamma-delta; D049452:Green Fluorescent Proteins