Type 1 Responses of Human Vγ9Vδ2 T Cells to Influenza A Viruses

Abstract

␥␦ T cells are essential constituents of antimicrobial and antitumor defenses. We have recently reported that phosphoantigen isopentenyl pyrophosphate (IPP)-expanded human V␥9V␦2 T cells participated in antiinfluenza 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 ␥␦ T cells to influenza virus. In this study, we found that V␥9V␦2 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-␥). Besides their potent cytolytic activity against pandemic H1N1 virus-infected cells, IPP-activated ␥␦ T cells also had noncytolytic inhibitory effects on seasonal and pandemic H1N1 viruses via IFN-␥ 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 V␥9V␦2 T cells than human seasonal H1N1 virus. CCR5 mediated the migration of V␥9V␦2 T cells toward influenza virus-infected cells. Our findings suggest a novel therapeutic strategy of using phosphoantigens to boost the antiviral activities of human V␥9V␦2 T cells against influenza virus infection.

The interaction of influenza H5N1 viral hemagglutinin with sialic acid receptors leads to the activation of human γδ T cells

“…[12][13][14] Recent studies demonstrated that cd T cells can kill both human and avian influenza virus-infected monocyte-derived macrophages. 15,16 cd T cells from human peripheral blood mononuclear cells (PBMCs) can be activated by influenza A infection. 17 Human Vc9d2 T cells express both type 1 cytokines and chemokine receptors in response to influenza A virus infection and display cytolytic activity against pandemic H1N1 virus-infected cells.…”

γδ-T cells: an unpolished sword in human anti-infection immunity

“…23,24 Similarly to the contribution of murine cd-T cells during recovery after influenza-caused pneumonia, 25 the beneficial effects of human Vc9Vd2 cd-T cells against influenza virus infection have also recently been confirmed by our laboratory. 22,26,27 Through the direct killing of virus-infected cells and the production of antiviral cytokines, Vc9Vd2 cd-T cells can control infection by different strains of the influenza virus, such as human seasonal H1N1, pandemic H1N1, and the avian H5N1 and H9N2 viruses. 22,26,27 Moreover, these antiviral activities can be significantly improved by phosphoantigen stimulation, which confers sufficient protection on humanized mice to prevent lethal influenza virus infection.…”

“…22,26,27 Through the direct killing of virus-infected cells and the production of antiviral cytokines, Vc9Vd2 cd-T cells can control infection by different strains of the influenza virus, such as human seasonal H1N1, pandemic H1N1, and the avian H5N1 and H9N2 viruses. 22,26,27 Moreover, these antiviral activities can be significantly improved by phosphoantigen stimulation, which confers sufficient protection on humanized mice to prevent lethal influenza virus infection. 28 In addition, another group has shown that cd-T cells can initiate efficient adaptive immunity through processing and presenting influenza virus-derived peptides to CD4 1 and CD8 1 T cells.…”

“…Similarly to its role in HCMV infection, IFN-c secreted from Vc9Vd2 cd-T cells inhibits influenza virus propagation. 26 In addition, IL-17 and tumor-necrosis factor-a secreted by various cd-T cell populations contribute to the control and elimination of several types of bacteria 45,96 and Plasmodium falciparum. 51 Recently, IL-22 has been suggested as a potent anti-infection cytokine in the cd-T cell-mediated anti-infection immune response by some reports.…”

“…101,103 Similarly to other sentinel cells, cd-T cells also secrete chemokines such as CCL2, CCL3 and CCL4 to recruit pro-inflammatory neutrophils to accelerate the elimination of pathogens and the repair of damaged tissues. 26 APC function. In addition to their direct anti-infection activities, human cd-T cells act as professional APCs and take up, process and present pathogen-related antigens from both free viral particles 29 and infected cells 57,105 to other effector immune cells.…”