title: Lysis of HIV-1-infected autologous CD4+ primary T cells by interferon-alpha-activated NK cells requires NKp46 and NKG2D.
abstract: OBJECTIVE
  Autologous HIV-1-infected CD4 primary T cells (aHIVCD4) have been shown to be largely resistant to natural killer (NK)-cell-mediated lysis because of viral strategies of immune evasion. We have previously shown that a preactivation of NK cells with plasmacytoid dendritic cells can significantly augment lysis of aHIVCD4 through a mechanism dependent on interferon-alpha (IFN-α).
  
  
  METHODS
  The goal of the present study is to identify the specific NK-activating receptors involved in NK lysis of aHIVCD4 following IFN-α activation.
  
  
  METHODS
  Peripheral blood mononuclear cells (PBMC) were incubated with aHIVCD4 to induce the secretion of endogenous levels of IFN-α and drive NK activation. We then utilized a standard chromium lysis assay to assess the degree of IFN-α-activated lysis of aHIVCD4 in the presence or absence of masking antibodies to a panel of NK-activating receptors and co-receptors.
  
  
  RESULTS
  Direct recognition of HIV-1-infected, but not uninfected, autologous CD4 primary T cells by PBMC induced the secretion IFN-α (median 2280 pg/ml, P < 0.001, n = 9) that, in turn, activated NK cells (P < 0.001, n = 12) and significantly increased their cytolytic potential against aHIVCD4 (P < 0.01, n = 12). The masking of NKp46 (P < 0.01, n = 8) and NKG2D (P < 0.05, n = 8), but not 2B4, NTBA, NKp30 or NKp44, significantly reduced IFN-α-activated lysis of aHIVCD4.
  
  
  CONCLUSIONS
  Taken together, these results demonstrate that endogenous levels of IFN-α secreted by plasmacytoid dendritic cells induce NK cells to lyse aHIVCD4 via the engagement of NKp46 and NKG2D.
authors.affiliation: aHIV Immunopathogenesis Laboratory, The Wistar Institute, Philadelphia, Pennsylvania, USA bUnit of Clinical and Experimental Immunology, Humanitas Clinical and Research Center, Rozzano cDepartment of Medical Biotechnologies and Translational Medicine, University of Milan, Milan, Italy.
authors.forename: Costin
authors.initials: C
authors.lastname: Tomescu
authors.forename: Domenico
authors.initials: D
authors.lastname: Mavilio
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Montaner
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000821:virology*; D002478:Cells, Cultured; D003601:Cytotoxicity Tests, Immunologic; D003602:Cytotoxicity, Immunologic; D015658:HIV Infections / Q000276:immunology* / Q000821:virology; D015497:HIV-1 / Q000254:growth & development; D006801:Humans; D016898:Interferon-alpha / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000276:immunology*; D055655:NK Cell Lectin-Like Receptor Subfamily K / Q000378:metabolism*; D055627:Natural Cytotoxicity Triggering Receptor 1 / Q000378:metabolism*
chemical_list: D016898:Interferon-alpha; C527085:KLRK1 protein, human; C112260:NCR1 protein, human; D055655:NK Cell Lectin-Like Receptor Subfamily K; D055627:Natural Cytotoxicity Triggering Receptor 1