Interferon-alpha-dependent and -independent participation of accessory cells in natural killer cell-mediated lysis of HSV-1-infected fibroblasts.
Human natural killer (NK) cells require an HLA-DR+ accessory cell (AC) population to lyse herpes simplex virus-type 1 (HSV-1)-infected fibroblasts (HSV-Fs) but not K562 target cells. It has been postulated that ACs may function by producing interferon-alpha (IFN-alpha), which stimulates NK cells. Using a sequential enrichment protocol, ACs were found to coenrich with the interferon-producing cells (IPCs). Treatment of the ACs with a protein synthesis inhibitor, emetine, inhibited both their IFN production and AC function, results that support a central role for IFN in AC activity. In contrast, when the arginine analogue canavanine was added to NK assays, no IFN-alpha was produced and NK(HSV-Fs) activity was only partially inhibited. Consistent with IFN-independent AC function, treatment with either polyclonal sheep or bovine anti-IFN-alpha neutralized all the IFN-alpha produced during the NK assays but caused either no or partial reduction of NK(HSV-Fs) activity, respectively. However, when limiting numbers of ACs were used, the bovine antiserum neutralized both IFN-alpha and NK(HSV-Fs) activity. We further found that HLA-DR+ cells are required for cell clustering, suggesting a role for cell contact. Finally, fixation of activated ACs prevented the accessory function. Together, these results demonstrate that ACs can provide help to NK cells in both IFN-alpha-dependent and -independent manners.
Feldman
M
M
Department of Laboratory Medicine and Pathology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103.
Howell
D
D
Fitzgerald-Bocarsly
P
P
D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology*; D002172:Canavanine / Q000494:pharmacology; D002417:Cattle; D003602:Cytotoxicity, Immunologic; D004640:Emetine / Q000494:pharmacology; D006684:HLA-DR Antigens / Q000032:analysis; D006561:Herpes Simplex / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D016898:Interferon-alpha / Q000276:immunology*; D007694:Killer Cells, Natural / Q000276:immunology*; D008212:Lymphocyte Depletion; D012756:Sheep; D018139:Simplexvirus / Q000276:immunology
D006684:HLA-DR Antigens; D016898:Interferon-alpha; D002172:Canavanine; D004640:Emetine