title: Type 1 responses of human Vγ9Vδ2 T cells to influenza A viruses.
abstract: γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection.
authors.affiliation: Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Qin
authors.forename: Yinping
authors.initials: Y
authors.lastname: Liu
authors.forename: Jian
authors.initials: J
authors.lastname: Zheng
authors.forename: Iris H Y
authors.initials: IH
authors.lastname: Ng
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.forename: Kwok-Tai
authors.initials: KT
authors.lastname: Lam
authors.forename: Huawei
authors.initials: H
authors.lastname: Mao
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.forename: J S Malik
authors.initials: JS
authors.lastname: Peiris
authors.forename: Yu-Lung
authors.initials: YL
authors.lastname: Lau
authors.forename: Wenwei
authors.initials: W
authors.lastname: Tu
mesh_terms: D002478:Cells, Cultured; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic; D045782:Hemiterpenes / Q000378:metabolism; D006801:Humans; D007155:Immunologic Factors / Q000378:metabolism; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology*; D053124:Influenza A Virus, H5N1 Subtype / Q000276:immunology; D053127:Influenza A Virus, H9N2 Subtype / Q000276:immunology; D009943:Organophosphorus Compounds / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000032:analysis*; D016176:T-Lymphocyte Subsets / Q000737:chemistry / Q000276:immunology*
chemical_list: D016207:Cytokines; D045782:Hemiterpenes; D007155:Immunologic Factors; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; C004809:isopentenyl pyrophosphate