Phosphoantigen-expanded Human Gammadelta T Cells Display Potent Cytotoxicities Towards Human and Avian Influenza Virus-infected Monocyte-derived Macrophages

Abstract

Background. Influenza virus is a cause of substantial annual morbidity and mortality worldwide. Potential for the emergence of a new pandemic strain, e.g. avian influenza virus, is a major concern. Currently available vaccines and anti-influenza drugs have limited effectiveness for influenza infections, especially for new pandemic strains. Therefore, there is an acute need for developing alternative strategies for influenza therapy. γδ-T cells have potent antiviral activities against different viruses. However, no data are available for 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 human (H1N1) and avian (H9N2 and H5N1) influenza virus-infected MDMs and significantly inhibited viral replication. The cytotoxicity of Vγ9Vδ2-T cells against influenza virus-infected MDMs was dependent on NKG2D activation, and mediated by Fas-FasL and perforin-granzyme B pathways. Conclusion. Our study suggests a potentially novel therapeutic approach for seasonal, zoonotic avian and pandemic influenza by using phosphoantigens to activate γδ-T cells against influenza infections.