Cooperation between CD16(Leu-11b)+ NK cells and HLA-DR+ cells in natural killing of herpesvirus-infected fibroblasts.
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.
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Division of Infectious Diseases, Joseph Stokes, Jr. Research Institute, Children's Hospital of Philadelphia, PA 19104.
Bandyopadhyay
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Miller
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Starr
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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*
D000943:Antigens, Differentiation; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007370:Interferon Type I