title: Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses.
abstract: BACKGROUND
  Influenza virus is a cause of substantial annual morbidity and mortality worldwide. The potential emergence of a new pandemic strain (eg, avian influenza virus) is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza virus infections, especially for new pandemic strains. Therefore, there is an acute need to develop alternative strategies for influenza therapy. gammadelta T cells have potent antiviral activities against different viruses, but no data are available concerning their antiviral activity against influenza viruses.
  
  
  METHODS
  In this study, we used virus-infected primary human monocyte-derived macrophages (MDMs) to examine the antiviral activity of phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vgamma9Vdelta2 T cells against influenza viruses.
  
  
  RESULTS
  Vgamma9Vdelta2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vgamma9Vdelta2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vgamma9Vdelta2 T cells against influenza virus-infected MDMs was dependent on NKG2D activation and was mediated by Fas-Fas ligand and perforin-granzyme B pathways.
  
  
  CONCLUSIONS
  Our findings suggest a potentially novel therapeutic approach to seasonal, zoonotic avian, and pandemic influenza-the use of phosphoantigens to activate gammadelta T cells against influenza virus infections.
authors: Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Special Administrative Region, Hong Kong, China.
authors: Gang
authors: G
authors: Qin
authors: Huawei
authors: H
authors: Mao
authors: Jian
authors: J
authors: Zheng
authors: Sin Fun
authors: SF
authors: Sia
authors: Yinping
authors: Y
authors: Liu
authors: Ping-Lung
authors: PL
authors: Chan
authors: Kwok-Tai
authors: KT
authors: Lam
authors: J S Malik
authors: JS
authors: Peiris
authors: Yu-Lung
authors: YL
authors: Lau
authors: Wenwei
authors: W
authors: Tu
mesh_terms: D000818:Animals; D003602:Cytotoxicity, Immunologic; D005786:Gene Expression Regulation / Q000502:physiology; D053804:Granzymes / Q000378:metabolism; D045782:Hemiterpenes; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D053124:Influenza A Virus, H5N1 Subtype / Q000502:physiology*; D053127:Influenza A Virus, H9N2 Subtype / Q000502:physiology*; D008264:Macrophages / Q000821:virology; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000235:genetics / Q000378:metabolism; D009943:Organophosphorus Compounds; D054353:Perforin / Q000378:metabolism; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism
chemical_list: C491901:FAS protein, human; D045782:Hemiterpenes; C527085:KLRK1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D009943:Organophosphorus Compounds; D016692:Receptors, Antigen, T-Cell, gamma-delta; D019014:fas Receptor; D054353:Perforin; C004809:isopentenyl pyrophosphate; D053804:Granzymes