Department of Paediatrics and Adolescent Medicine, University of Hong Kong, Hong Kong SAR, China.
J Virol. 2011 Oct;85(19):10109-16. doi: 10.1128/JVI.05341-11. Epub 2011 Jul 13.
γδ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human Vγ9Vδ2 T cells participated in anti-influenza virus immunity by efficiently killing both human and avian influenza virus-infected monocyte-derived macrophages (MDMs) in vitro. However, little is known about the noncytolytic responses and trafficking program of γδ T cells to influenza virus. In this study, we found that Vγ9Vδ2 T cells expressed both type 1 cytokines and chemokine receptors during influenza virus infection, and IPP-expanded cells had a higher capacity to produce gamma interferon (IFN-γ). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated γδ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-γ but had no such effects on avian H5N1 or H9N2 virus. Avian H5N1 and H9N2 viruses induced significantly higher CCL3, CCL4, and CCL5 production in Vγ9Vδ2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of Vγ9Vδ2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human Vγ9Vδ2 T cells against influenza virus infection.
γδ T 细胞是抗微生物和抗肿瘤防御的重要组成部分。我们最近报道，磷酸抗原异戊烯焦磷酸（IPP）扩增的人 Vγ9Vδ2 T 细胞通过有效杀伤体外感染的人源和禽源流感病毒的单核细胞衍生的巨噬细胞（MDM）参与抗流感病毒免疫。然而，γδ T 细胞对流感病毒的非细胞裂解反应和归巢程序知之甚少。在这项研究中，我们发现 Vγ9Vδ2 T 细胞在流感病毒感染过程中表达 1 型细胞因子和趋化因子受体，并且 IPP 扩增的细胞具有更高的产生γ干扰素（IFN-γ）的能力。除了对大流行 H1N1 病毒感染细胞具有强大的细胞毒性活性外，IPP 激活的 γδ T 细胞还通过 IFN-γ对季节性和大流行 H1N1 病毒具有非细胞毒性抑制作用，但对禽源 H5N1 或 H9N2 病毒没有这种作用。禽源 H5N1 和 H9N2 病毒诱导 Vγ9Vδ2 T 细胞产生明显更高水平的 CCL3、CCL4 和 CCL5，高于人季节性 H1N1 病毒。CCR5 介导 Vγ9Vδ2 T 细胞向流感病毒感染细胞的迁移。我们的研究结果表明，使用磷酸抗原来增强人 Vγ9Vδ2 T 细胞对流感病毒感染的抗病毒活性是一种新的治疗策略。
