title: Preferential Th1 cytokine profile of phosphoantigen-stimulated human Vγ9Vδ2 T cells.
abstract: Human Vγ9Vδ2 T cells recognise pyrophosphate-based antigens (phosphoantigens) and have multiple functions in innate and adaptive immunity, including a unique ability to activate other cells of the immune system. We used flow cytometry and ELISA to define the early cytokine profiles of Vγ9Vδ2 T cells stimulated in vitro with isopentenyl pyrophosphate (IPP) and (E)-4-hydroxy-3-methyl-but-2 enyl pyrophosphate (HMB-PP) in the absence and presence of IL-2 and IL-15. We show that fresh Vγ9Vδ2 T cells produce interferon-γ (IFN-γ) and tumour necrosis factor-α (TNF-α) within 4 hours of stimulation with phosphoantigen, but neither IL-10, IL-13, nor IL-17 was detectable up to 72 hours under these conditions. Cytokine production was not influenced by expression or lack, thereof, of CD4 or CD8. Addition of IL-2 or IL-15 caused expansion of IFN-γ-producing Vγ9Vδ2 T cells, but did not enhance IFN-γ secretion after 24-72 hours. Thus, phosphoantigen-stimulated Vγ9Vδ2 T cells have potential as Th1-biasing adjuvants for immunotherapy.
authors.affiliation: Department of Immunology and Institute of Molecular Medicine, Trinity College Dublin, St. James's Hospital, Dublin 8, Ireland.
authors.forename: Margaret R
authors.initials: MR
authors.lastname: Dunne
authors.forename: Bozgana A
authors.initials: BA
authors.lastname: Mangan
authors.forename: Laura
authors.initials: L
authors.lastname: Madrigal-Estebas
authors.forename: Derek G
authors.initials: DG
authors.lastname: Doherty
mesh_terms: D000941:Antigens / Q000276:immunology; D016207:Cytokines / Q000378:metabolism*; D011756:Diphosphates / Q000276:immunology; D045782:Hemiterpenes / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000096:biosynthesis; D007378:Interleukins / Q000096:biosynthesis / Q000494:pharmacology; D009943:Organophosphorus Compounds / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: C443995:4-hydroxy-3-methylbut-2-enyl pyrophosphate; D000941:Antigens; D016207:Cytokines; D011756:Diphosphates; D045782:Hemiterpenes; D007378:Interleukins; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C521523:T-cell receptor Vdelta2, human; C521522:T-cell receptor Vgamma9, human; D014409:Tumor Necrosis Factor-alpha; C004809:isopentenyl pyrophosphate; D007371:Interferon-gamma