Intracellular IFN-gamma expression in natural killer cells precedes lung CD8+ T cell recruitment during respiratory syncytial virus infection

J Gen Virol. 1998 Nov;79 ( Pt 11):2593-601. doi: 10.1099/0022-1317-79-11-2593.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / pathology
  • Cell Movement / immunology
  • Cytotoxicity, Immunologic*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / immunology*
  • Killer Cells, Natural / immunology*
  • Mice
  • Mice, Inbred BALB C
  • Pneumovirus / immunology
  • Respiratory Syncytial Virus Infections / immunology*
  • Respiratory Syncytial Virus Infections / pathology


  • Interferon-gamma