title: Activation of natural interferon-alpha producing cells by apoptotic U937 cells combined with lupus IgG and its regulation by cytokines.
abstract: We recently demonstrated that IgG from patients with systemic lupus erythematosus (SLE) in combination with U937 cells made apoptotic by UV-irradiation, can induce interferon-alpha (IFN-alpha) production in normal peripheral blood mononuclear cells (PBMC). In the present study we show by flow cytometry that the actual IFN-alpha producing cells (IPC) among PBMC had the same phenotype (HLA-DR+, CD4+, CD11b-, CD11c-, CD14-, CD19-, CD32-, CD36+, CD40+, CD45RA+, CD68+, CD83+, CD86-, IL-3R+ and IL-10R-) and low frequency (approximately 2/10(4)PBMC) as the IPC activated by Herpes simplex virus type I. Consequently, these cells correspond to the natural IPC, also described as type 2 precursor dendritic cells. We also demonstrated that cytokines of possible importance in the pathogenesis in SLE had effects on the IFN-alpha production. Specifically, the IFN-alpha production was strongly increased by the type I IFNs, IFN-alpha and -beta, but markedly inhibited by IL-10 and also to some extent by TFN-alpha. In contrast, the cytokines IFN-gamma, IL-6, TGF-beta and GM-CSF had no clear effects. No production of IL-10 was detected in PBMC stimulated by apoptotic U937 cells and SLE IgG. These results may explain the cause of the ongoing IFN-alpha production in SLE patients and its relation to the autoimmune process.
authors.affiliation: Department of Medical Sciences, Section of Rheumatology, University Hospital, Uppsala, Sweden. ullvi.bave@medsci.uu.se
authors.forename: U
authors.initials: U
authors.lastname: Båve
authors.forename: H
authors.initials: H
authors.lastname: Vallin
authors.forename: G V
authors.initials: GV
authors.lastname: Alm
authors.forename: L
authors.initials: L
authors.lastname: Rönnblom
mesh_terms: D000293:Adolescent; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D001323:Autoantibodies / Q000502:physiology*; D002478:Cells, Cultured; D016207:Cytokines / Q000502:physiology*; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007074:Immunoglobulin G / Q000502:physiology*; D016130:Immunophenotyping; D016898:Interferon-alpha / Q000096:biosynthesis / Q000378:metabolism*; D016753:Interleukin-10 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008177:Lupus Vulgaris / Q000276:immunology*; D008297:Male; D012542:Scattering, Radiation; D020298:U937 Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism / Q000528:radiation effects; D014466:Ultraviolet Rays
chemical_list: D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; D016753:Interleukin-10