Human mononuclear cells which produce interferon-alpha during NK(HSV-FS) assays are HLA-DR positive cells distinct from cytolytic natural killer effectors.
Human mononuclear cells were previously shown to produce interferon-alpha (IFN) during 14 hr assays using herpes simplex virus type-1 infected fibroblasts [NK(HSV-FS)]. In this study, we have compared the effectors responsible for mediating NK(HSV-FS) cytolytic activity to those which produce IFN-alpha. Both activities were found to reside in non-adherent fractions, negative for non-specific esterase-staining cells. Like cells mediating NK cytolytic activity, IFN-alpha producing cells were found in light density Percoll gradient fractions. However, although NK(HSV-FS) and IFN production were largely overlapping, peak IFN production was consistently found in fractions slightly less dense than peak NK(HSV-FS) activity. IFN production was greatly augmented in fractions enriched for dendritic cells on hypertonic metrizamide gradients. The cells which produce IFN-alpha were phenotypically distinct from cytolytic NK effector cells: they lacked the Leu-11, Leu-7 and NKH1 cell surface markers shown to be present on both NK(HSV-FS) and NK(K562) effector cells. In addition, the IFN-alpha producing cells were found to be negative for a number of other markers characteristic of T cells, B cells or macrophages but were positive for Ia and HLA. The cells which produced IFN in response to UV-inactivated HSV antigen and to HSV-infected Raji cells were also found to be Leu-11 negative, and Ia positive. We conclude that the cells which produce IFN in response to HSV are a light density, Ia positive population which are distinct from NK cytolytic effector cells and co-purify with cells bearing a dendritic morphology. These results support our earlier findings that NK(HSV-FS) activity and IFN production are independent of one another and can segregate independently in vivo.
Fitzgerald-Bocarsly
P
P
Department of Pathology, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark 07103-2757.
Feldman
M
M
Mendelsohn
M
M
Curl
S
S
Lopez
C
C
D000911:Antibodies, Monoclonal / Q000276:immunology; D000943:Antigens, Differentiation / Q000032:analysis; D002469:Cell Separation; D003602:Cytotoxicity, Immunologic; D006681:HLA-D Antigens / Q000032:analysis*; D006684:HLA-DR Antigens / Q000032:analysis*; D006801:Humans; D007111:Immunity, Cellular; D007113:Immunity, Innate; D066298:In Vitro Techniques; D007370:Interferon Type I / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000502:physiology*; D007963:Leukocytes, Mononuclear / Q000502:physiology*; D018139:Simplexvirus
D000911:Antibodies, Monoclonal; D000943:Antigens, Differentiation; D006681:HLA-D Antigens; D006684:HLA-DR Antigens; D007370:Interferon Type I