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

ABSTRACT 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.

[1]  M. Eberl,et al.  Prolonged antigen survival and cytosolic export in cross-presenting human γδ T cells , 2010, Proceedings of the National Academy of Sciences.

[2]  Y. Guan,et al.  Cytotoxic T Lymphocytes Established by Seasonal Human Influenza Cross-React against 2009 Pandemic H1N1 Influenza Virus , 2010, Journal of Virology.

[3]  J. Peiris,et al.  Inhibition of Human Natural Killer Cell Activity by Influenza Virions and Hemagglutinin , 2010, Journal of Virology.

[4]  L. Finelli,et al.  Emergence of a novel swine-origin influenza A (H1N1) virus in humans. , 2009, The New England journal of medicine.

[5]  Yan Zhou,et al.  The functional impairment of natural killer cells during influenza virus infection , 2009, Immunology and cell biology.

[6]  J. Peiris,et al.  A novel H1N1 virus causes the first pandemic of the 21st century , 2009, European journal of immunology.

[7]  Kwok-Hung Chan,et al.  Virologically confirmed population-based burden of hospitalization caused by influenza A and B among children in Hong Kong. , 2009, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[8]  Y. Lau,et al.  Efficient Induction and Expansion of Human Alloantigen-Specific CD8 Regulatory T Cells from Naive Precursors by CD40-Activated B Cells1 , 2009, The Journal of Immunology.

[9]  J. Peiris,et al.  Phosphoantigen-Expanded Human γδ T Cells Display Potent Cytotoxicity against Monocyte-Derived Macrophages Infected with Human and Avian Influenza Viruses , 2009, The Journal of infectious diseases.

[10]  Y. Lau,et al.  Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis , 2009, Journal of Virology.

[11]  M. Hirokawa,et al.  Skewed T cell receptor repertoire of Vδ1+ γδ T lymphocytes after human allogeneic haematopoietic stem cell transplantation and the potential role for Epstein–Barr virus‐infected B cells in clonal restriction , 2007 .

[12]  C. Hess,et al.  Investigation of alloreactive NK cells in mixed lymphocyte reactions using paraformaldehyde-silenced target cells. , 2007, Journal of immunological methods.

[13]  H. Valantine,et al.  T-Cell Immunity to Subclinical Cytomegalovirus Infection Reduces Cardiac Allograft Disease , 2006, Circulation.

[14]  M. Bonneville,et al.  Human Vγ9Vδ2 T cells : promising new leads for immunotherapy of infections and tumors , 2006 .

[15]  Y. Lau,et al.  Differential Expression of Chemokines and Their Receptors in Adult and Neonatal Macrophages Infected with Human or Avian Influenza Viruses , 2006, The Journal of infectious diseases.

[16]  L. Lanier,et al.  Natural killer cells as an initial defense against pathogens , 2006, Current Opinion in Immunology.

[17]  Yoshihiro Kawaoka,et al.  Avian flu: Influenza virus receptors in the human airway , 2006, Nature.

[18]  W. Born,et al.  The function of γδ T cells in innate immunity , 2006 .

[19]  D. Lewis,et al.  Avian flu to human influenza. , 2006, Annual review of medicine.

[20]  G. D'offizi,et al.  Activation of Vγ9Vδ2 T cells by non-peptidic antigens induces the inhibition of subgenomic HCV replication , 2005, International immunology.

[21]  B. Moser,et al.  Professional Antigen-Presentation Function by Human γδ T Cells , 2005, Science.

[22]  H. de la Salle,et al.  Shared reactivity of Vδ2neg γδ T cells against cytomegalovirus-infected cells and tumor intestinal epithelial cells , 2005, The Journal of experimental medicine.

[23]  C. Agrati,et al.  Antiviral reactivities of γδ T cells , 2005, Microbes and Infection.

[24]  W. Ip,et al.  Distinct Maturation of, but Not Migration between, Human Monocyte-Derived Dendritic Cells upon Ingestion of Apoptotic Cells of Early or Late Phases 1 , 2004, The Journal of Immunology.

[25]  H. Klenk,et al.  Human and avian influenza viruses target different cell types in cultures of human airway epithelium. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[26]  H. Maecker,et al.  Persistent and Selective Deficiency of CD4+ T Cell Immunity to Cytomegalovirus in Immunocompetent Young Children1 , 2004, The Journal of Immunology.

[27]  J. Peiris,et al.  Re-emergence of fatal human influenza A subtype H5N1 disease , 2004, The Lancet.

[28]  M. Ferrarini,et al.  Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type‐1/‐2 γ δ T lymphocytes , 2002 .

[29]  R. Webster,et al.  Lethal H5N1 influenza viruses escape host anti-viral cytokine responses , 2002, Nature Medicine.

[30]  O. Janssen,et al.  Patterns of Chemokine Receptor Expression on Peripheral Blood γδ T Lymphocytes: Strong Expression of CCR5 Is a Selective Feature of Vδ2/Vγ9 γδ T Cells1 , 2002, The Journal of Immunology.

[31]  M. Simon,et al.  Adaptive Immune Response of Vγ2Vδ2+ T Cells During Mycobacterial Infections , 2002, Science.

[32]  M. Ferrarini,et al.  Skewing of cytotoxic activity and chemokine production, but not of chemokine receptor expression, in human type-1/-2 gamma delta T lymphocytes. , 2002, European journal of immunology.

[33]  M. Caligiuri,et al.  The biology of human natural killer-cell subsets. , 2001, Trends in immunology.

[34]  B. Spellberg,et al.  Type 1/Type 2 immunity in infectious diseases. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[35]  G. Karupiah,et al.  Chemokines and chemokine receptors in infectious diseases , 1999, Immunology and cell biology.

[36]  F. Poccia,et al.  Phosphoantigen-reactive Vgamma9Vdelta2 T lymphocytes suppress in vitro human immunodeficiency virus type 1 replication by cell-released antiviral factors including CC chemokines. , 1999, The Journal of infectious diseases.

[37]  Y. Guan,et al.  Molecular characterization of H9N2 influenza viruses: were they the donors of the "internal" genes of H5N1 viruses in Hong Kong? , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[38]  D. F. Barber,et al.  Primary γδ Cell Clones Can Be Defined Phenotypically and Functionally as Th1/Th2 Cells and Illustrate the Association of CD4 with Th2 Differentiation , 1998, The Journal of Immunology.

[39]  P. Allavena,et al.  Differential Expression of Chemokine Receptors and Chemotactic Responsiveness of Type 1 T Helper Cells (Th1s) and Th2s , 1998, The Journal of experimental medicine.

[40]  F. Poccia,et al.  CD94/NKG2 inhibitory receptor complex modulates both anti-viral and anti-tumoral responses of polyclonal phosphoantigen-reactive V gamma 9V delta 2 T lymphocytes. , 1997, Journal of immunology.

[41]  B. Bloom,et al.  Natural and synthetic non-peptide antigens recognized by human γδ T cells , 1995, Nature.

[42]  Y. Tanaka,et al.  Natural and synthetic non-peptide antigens recognized by human gamma delta T cells. , 1995, Nature.

[43]  M. Brenner,et al.  Recognition and destruction of virus-infected cells by human gamma delta CTL. , 1994, Journal of immunology.

[44]  D. J. Arora,et al.  Concentration and purification of influenza virus from allantoic fluid. , 1985, Analytical biochemistry.