title: Distinct roles of NK cells in viral immunity during different phases of acute Friend retrovirus infection.
abstract: BACKGROUND
  In many virus infections natural killer (NK) cells are critical for the rapid containment of virus replication. Polymorphisms in NK cell receptors as well as viral escape from NK cell responses are associated with pathogenesis and viral loads in HIV-infected individuals, emphasizing their importance in retroviral immunity. In contrast, NK cells of LCMV-infected mice dampened virus-specific T cell responses resulting in impaired virus control. Thus, the exact role of NK cells during different phases of viral infections remains elusive. In this study we characterized the NK cell response at different time points of an acute retroviral infection by using the Friend retrovirus (FV) mouse model.
  
  
  RESULTS
  Depletion of NK1.1⁺ cells during the initial phase of FV infection (3 to 4 days post infection) resulted in increased viral loads, which correlated with enhanced target cell killing and elevated NK cell effector functions. At days 7 to 15 post infection, NK and NKT cells did not contribute to anti-retroviral immunity. In the transition phase between acute and chronic infection (30 days post infection), NK and NKT cells exhibited an inhibitory role and their depletion resulted in reduced viral loads and significantly improved FV-specific CD8⁺ T cell responses.
  
  
  CONCLUSIONS
  Our results demonstrate an opposed activity of NK cells during retroviral infection. They were protective in the initial phase of infection, when adaptive T cell responses were not yet detectable, but were dispensable for viral immunity after T cell expansion. At later time points they exhibited regulatory functions in inhibiting virus-specific CD8⁺ T cell responses.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Littwitz
authors.forename: Sandra
authors.initials: S
authors.lastname: Francois
authors.forename: Ulf
authors.initials: U
authors.lastname: Dittmer
authors.affiliation: Institute for Virology of the University Hospital in Essen, University of Duisburg-Essen, Essen, Germany. Kathrin.gibbert@uni-due.de.
authors.forename: Kathrin
authors.initials: K
authors.lastname: Gibbert
mesh_terms: D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D005622:Friend murine leukemia virus / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D007942:Leukemia, Experimental / Q000276:immunology*; D047589:Leukocyte Reduction Procedures; D051379:Mice; D055611:Natural Killer T-Cells / Q000276:immunology*; D012192:Retroviridae Infections / Q000276:immunology*; D013997:Time Factors; D014412:Tumor Virus Infections / Q000276:immunology*; D019562:Viral Load