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J Infect Dis. Phosphoantigen-Expanded Human gammadelta T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human an

Giuseppe

Emeritus
J Infect Dis. 2009 Aug 5. [Epub ahead of print]

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

Qin G, Mao H, Zheng J, Sia SF, Liu Y, Chan PL, Lam KT, Peiris JS, Lau YL, Tu W. - Departments of 1Paediatrics and Adolescent Medicine and 2Microbiology, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong Special Administrative Region, and 3Joint Research Centre of the West China Second University Hospital, Sichuan University, Chengdu, and the Department of Paediatrics and Adolescent Medicine, University of Hong Kong, China.


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.

PMID: 19656068 [PubMed - as supplied by publisher]
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