Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses
Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses
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DOI：
10.1086/605413
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发表时间：
2009-09-15
影响因子：
6.4
通讯作者：
Tu, Wenwei
中科院分区：
文献类型：
--
作者：
Qin, Gang;Mao, Huawei;Tu, Wenwei
背景流感病毒是全世界每年发病率和死亡率很高的原因。一种新的大流行毒株（如禽流感病毒）的潜在出现是一个主要问题。目前可用的疫苗和抗流感药物对流感病毒感染的有效性有限，特别是对新的大流行毒株。因此，迫切需要开发用于流感治疗的替代策略。γ δ T细胞对不同的病毒具有有效的抗病毒活性，但是没有关于它们对流感病毒的抗病毒活性的数据。在这项研究中，我们使用病毒感染的原代人单核细胞衍生的巨噬细胞（MDM）来检测磷酸化抗原异戊烯焦磷酸（IPP）扩增的人V γ 9V δ 2 T细胞对流感病毒的抗病毒活性。通过IPP从外周血单核细胞选择性地活化和扩增V γ 9V δ 2 T细胞。IPP扩增的V γ 9V δ 2 T细胞有效地杀死感染了人（H1N1）或禽（H9 N2或H5 N1）流感病毒的MDM，并显著抑制病毒复制。V γ 9 V delta 2 T细胞对流感病毒感染的MDM的细胞毒作用依赖于NKG 2D活化，并通过Fas-Fas配体和穿孔素-颗粒酶B途径介导。我们的研究结果表明，一种潜在的新的治疗方法，季节性，人畜共患禽流感，和大流行性流感的磷酸化抗原的使用，以激活γ δ T细胞对流感病毒感染。
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. gamma delta 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 V gamma 9V delta 2 T cells against influenza viruses.Results. V gamma 9V delta 2 T cells were selectively activated and expanded by IPP from peripheral blood mononuclear cells. IPP-expanded V gamma 9V delta 2 T cells efficiently killed MDMs infected with human (H1N1) or avian (H9N2 or H5N1) influenza virus and significantly inhibited viral replication. The cytotoxicity of V gamma 9V delta 2 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 gamma delta T cells against influenza virus infections.