Activation of natural interferon-α producing cells by apoptotic U937 cells combined with lupus IgG and its regulation by cytokines

被引:80
作者
Båve, U [1 ]
Vallin, H
Alm, GV
Rönnbolm, L
机构
[1] Univ Uppsala Hosp, Dept Med Sci, Rheumatol Sect, Uppsala, Sweden
[2] Biomed Ctr, Dept Vet Microbiol, Immunol Sect, Uppsala, Sweden
关键词
apoptosis; dendritic cells; lupus; interleukin-10; type I interferon;
D O I
10.1006/jaut.2001.0519
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
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 L 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-a 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-a production in SLE patients and its relation to the autoimmune process. (C) 2001 Academic Press.
引用
收藏
页码:71 / 80
页数:10
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