Activation of natural interferon-alpha producing cells by apoptotic U937 cells combined with lupus IgG and its regulation by cytokines.
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.
Båve
U
U
Department of Medical Sciences, Section of Rheumatology, University Hospital, Uppsala, Sweden. ullvi.bave@medsci.uu.se
Vallin
H
H
Alm
G V
GV
Rönnblom
L
L
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
D001323:Autoantibodies; D016207:Cytokines; D007074:Immunoglobulin G; D016898:Interferon-alpha; D016753:Interleukin-10