title: Cooperation between CD16(Leu-11b)+ NK cells and HLA-DR+ cells in natural killing of herpesvirus-infected fibroblasts.
abstract: We reported previously that natural killer (NK) cell-mediated lysis of cytomegalovirus-infected targets requires the presence of HLA-DR+ nonadherent peripheral blood mononuclear cells (NPBMC). In the present study we determined whether NK cell-mediated lysis of other herpesvirus-infected targets also requires HLA-DR+ cells. Depletion of either cluster designation (CD)16+ NK cells or HLA-DR+ cells from NPBMC significantly reduced their ability to lyse herpes simplex virus (HSV)- and varicella-zoster virus (VZV)-infected fibroblasts. When CD16- and HLA-DR- populations were mixed, lysis of both HSV- and VZV-infected targets was virtually completely restored, indicating that NK cells and HLA-DR+ cells were required for lysis to occur. Cell-free supernatants, obtained by incubating NPBMC or CD16- cells with HSV-o-VZV-infected targets, contained antiviral activity and stimulated HLA-DR-cells to mediate lysis of corresponding virus-infected targets. The addition of anti-interferon-alpha to supernatants abolished their ability to stimulate lysis. Thus, secretion of interferon-alpha by HLA-DR+ cells contributes to NK cell-mediated lysis of herpesvirus-infected targets.
authors.affiliation: Division of Infectious Diseases, Joseph Stokes, Jr. Research Institute, Children's Hospital of Philadelphia, PA 19104.
authors.forename: S H
authors.initials: SH
authors.lastname: Oh
authors.forename: S
authors.initials: S
authors.lastname: Bandyopadhyay
authors.forename: D S
authors.initials: DS
authors.lastname: Miller
authors.forename: S E
authors.initials: SE
authors.lastname: Starr
mesh_terms: D000943:Antigens, Differentiation / Q000032:analysis; D002644:Chickenpox / Q000276:immunology*; D003602:Cytotoxicity, Immunologic; D005347:Fibroblasts; D006681:HLA-D Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006561:Herpes Simplex / Q000276:immunology*; D014645:Herpesvirus 3, Human / Q000276:immunology; D006801:Humans; D007113:Immunity, Innate; D007370:Interferon Type I / Q000502:physiology; D007694:Killer Cells, Natural / Q000276:immunology*; D007963:Leukocytes, Mononuclear / Q000276:immunology*
chemical_list: D000943:Antigens, Differentiation; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007370:Interferon Type I