Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses

J Infect Dis. 2009 Sep 15;200(6):858-65. doi: 10.1086/605413.


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.

Conclusion: 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.

MeSH terms

  • Animals
  • Cytotoxicity, Immunologic
  • Gene Expression Regulation / physiology
  • Granzymes / metabolism
  • Hemiterpenes*
  • Humans
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Influenza A Virus, H5N1 Subtype / physiology*
  • Influenza A Virus, H9N2 Subtype / physiology*
  • Macrophages / virology
  • NK Cell Lectin-Like Receptor Subfamily K / genetics
  • NK Cell Lectin-Like Receptor Subfamily K / metabolism
  • Organophosphorus Compounds*
  • Perforin / metabolism
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • fas Receptor / metabolism


  • FAS protein, human
  • Hemiterpenes
  • KLRK1 protein, human
  • NK Cell Lectin-Like Receptor Subfamily K
  • Organophosphorus Compounds
  • Receptors, Antigen, T-Cell, gamma-delta
  • fas Receptor
  • Perforin
  • isopentenyl pyrophosphate
  • Granzymes