Phosphoantigen-expanded human gammadelta T cells display potent cytotoxicity against monocyte-derived macrophages infected with human and avian influenza viruses.
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.
Qin
Gang
G
Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Special Administrative Region, Hong Kong, China.
Mao
Huawei
H
Zheng
Jian
J
Sia
Sin Fun
SF
Liu
Yinping
Y
Chan
Ping-Lung
PL
Lam
Kwok-Tai
KT
Peiris
J S Malik
JS
Lau
Yu-Lung
YL
Tu
Wenwei
W
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
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