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Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses

Gang Qin, Huawei Mao, Jian Zheng, Sin Fun Sia, Yinping Liu, Ping-Lung Chan, Kwok-Tai Lam, J. S. Malik Peiris, Yu-Lung Lau and Wenwei Tu
The Journal of Infectious Diseases
Vol. 200, No. 6 (15 September 2009), pp. 858-865
Published by: Oxford University Press
Stable URL: http://www.jstor.org/stable/27794151
Page Count: 8
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Phosphoantigen-Expanded Human γδ T Cells
              Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human
              and Avian Influenza Viruses
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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. γδ 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 Vγ9Vδ2 T cells against influenza viruses. Results. Vγ9Vδ2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded Vγ9Vδ2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2 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 γδ T cells against influenza virus infections.

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