title: NK cells regulate CD8+ T cell priming and dendritic cell migration during influenza A infection by IFN-γ and perforin-dependent mechanisms.
abstract: An effective immune response against influenza A infection depends on the generation of virus-specific T cells. NK cells are one of the first-line defenses against influenza A infection. We set out to delineate the role of NK cells in T cell immunity using a murine model of influenza A infection with A/PR/8/34. We show that early T cell recruitment mainly occurs in the posterior mediastinal lymph node (pMLN). Depletion of NK cells significantly impaired both dendritic cell (DC) and T cell recruitment into the pMLN. A similar reduction of T cell recruitment was observed when migration was blocked by pertussis toxin, suggesting that migration of pulmonary NK cells and DCs regulates cell recruitment to the pMLN. T cell recruitment was dependent on IFN-γ, and transfer of IFN-γ-competent naive NK cells into IFN-γ-/- mice restored T cell recruitment, whereas IFN-γ-deficient NK cells failed to do so. In addition, NK cell depletion reduced the uptake and transport of influenza A virus by DCs, and significantly impaired the virus-specific T cell response. Both IFN-γ-/- and perforin-/- mice showed reduced viral Ag transport by DCs, suggesting that the ability of NK cells to influence virus transport depends on IFN-γ and perforin. In summary, our data suggest that NK cells play a critical role in the initiation and shaping of the T cell response after influenza A infection.
authors.affiliation: Immunology Program, Centre for Life Sciences, National University of Singapore, Singapore 117456.
authors.forename: Moyar Qing
authors.initials: MQ
authors.lastname: Ge
authors.forename: Adrian W S
authors.initials: AW
authors.lastname: Ho
authors.forename: Yafang
authors.initials: Y
authors.lastname: Tang
authors.forename: Kenneth H S
authors.initials: KH
authors.lastname: Wong
authors.forename: Benson Y L
authors.initials: BY
authors.lastname: Chua
authors.forename: Stephan
authors.initials: S
authors.lastname: Gasser
authors.forename: David Michael
authors.initials: DM
authors.lastname: Kemeny
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000821:virology; D002460:Cell Line; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000276:immunology*; D003713:Dendritic Cells / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000276:immunology; D007371:Interferon-gamma / Q000502:physiology*; D007694:Killer Cells, Natural / Q000276:immunology* / Q000821:virology; D008198:Lymph Nodes / Q000276:immunology / Q000473:pathology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D009976:Orthomyxoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology; D052899:Pore Forming Cytotoxic Proteins / Q000502:physiology*
chemical_list: D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D007371:Interferon-gamma