title: A regulatory cross-talk between Vgamma9Vdelta2 T lymphocytes and mesenchymal stem cells.
abstract: The physiological functions of human TCRVgamma9Vdelta2(+) gammadelta lymphocytes reactive to non-peptide phosphoantigens contribute to cancer immunosurveillance and immunotherapy. However, their regulation by mesenchymal stem cells (MSC), multipotent and immunomodulatory progenitor cells able to infiltrate tumors, has not been investigated so far. By analyzing freshly isolated TCRVgamma9Vdelta2(+) lymphocytes and primary cell lines stimulated with synthetic phosphoantigen or B-cell lymphoma cell lines in the presence of MSC, we demonstrated that MSC were potent suppressors of gammadelta-cell proliferation, cytokine production and cytolytic responses in vitro. This inhibition was mediated by the COX-2-dependent production of prostaglandin E2 (PGE(2)) and by MSC through EP2 and EP4 inhibitory receptors expressed by Vgamma9Vdelta2 T lymphocytes. COX-2 expression and PGE(2) production by MSC were not constitutive, but were induced by IFN-gamma and TNF-alpha secreted by activated Vgamma9Vdelta2 T cells. This regulatory cross-talk between MSC and Vgamma9Vdelta2 T lymphocytes involving PGE(2) could be of importance for the antitumor and antimicrobial activities of gammadelta T cells.
authors.affiliation: INSERM, U.563, Centre de Physiopathologie de Toulouse-Purpan, Toulouse, France.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Martinet
authors.forename: Sandrine
authors.initials: S
authors.lastname: Fleury-Cappellesso
authors.forename: Mélanie
authors.initials: M
authors.lastname: Gadelorge
authors.forename: Gilles
authors.initials: G
authors.lastname: Dietrich
authors.forename: Philippe
authors.initials: P
authors.lastname: Bourin
authors.forename: Jean-Jacques
authors.initials: JJ
authors.lastname: Fournié
authors.forename: Rémy
authors.initials: R
authors.lastname: Poupot
mesh_terms: D002450:Cell Communication / Q000276:immunology*; D051546:Cyclooxygenase 2 / Q000276:immunology* / Q000378:metabolism; D015232:Dinoprostone / Q000096:biosynthesis / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000276:immunology* / Q000378:metabolism; D020239:Receptor Cross-Talk / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000037:antagonists & inhibitors / Q000276:immunology*; D018078:Receptors, Prostaglandin E / Q000276:immunology / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D016692:Receptors, Antigen, T-Cell, gamma-delta; D018078:Receptors, Prostaglandin E; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D015232:Dinoprostone