title: Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection.
abstract: Natural killer (NK) cells are recruited locally during the initial phases of virus infection and produce cytokines which may affect the subsequent emergence of specific T cells. In this study, cellular responses to primary respiratory syncytial virus (RSV) infection and after vaccination with individual viral proteins were investigated in BALB/c mice using the new NK cell antibody, DX5. Purified DX5+ cells caused lysis of YAC-1 cell targets. DX5+ cells did not express CD8, CD45R or MHC class II antigens. A small proportion of DX5+ cells co-expressed CD4 (10.3%) and CD3 (10.6%). Of the DX5+/CD4+ cells, the majority expressed the alpha/beta T cell receptor and less than 1% expressed the gamma/delta T cell receptor. During infection with RSV, lung DX5+/CD3- NK cells peaked on day 4 of primary infection and were the most numerous subset producing IFN-gamma, as determined by intracellular staining, at this time-point. Less than 1% of the DX5+ cells secreting IFN-gamma were CD4+. In the lungs of mice vaccinated with recombinant vaccinia virus expressing individual RSV proteins, increased NK cell cytotoxicity and IFN-gamma production correlated with increased numbers of CD8+ T cells. Mice with few NK cells subsequently had low CD8+ T cells and developed lung eosinophilia. IFN-gamma-producing NK cells therefore form a substantial component of the early cellular response to virus infection with important potential influences on the subsequent development of specific immunity.
authors.affiliation: Respiratory Medicine, National Heart and Lung Institute, Imperial College School of Medicine, Paddington, London, UK. t.hussell@ic.ac.uk
authors.forename: T
authors.initials: T
authors.lastname: Hussell
authors.forename: P J
authors.initials: PJ
authors.lastname: Openshaw
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002465:Cell Movement / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D018111:Pneumovirus / Q000276:immunology; D018357:Respiratory Syncytial Virus Infections / Q000276:immunology* / Q000473:pathology
chemical_list: D007371:Interferon-gamma