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 erythem atosus (SLE) in combination with U937 cells made apoptotic by UV-irradiatio n, can induce interferon-alpha (IFN-alpha) production in normal peripheral blood mononuclear cells (PBMC). In the present study we show by flow cytome try 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 (app roximately 2/10(4) PBMC) as the IPC activated by Herpes simplex virus type L Consequently, these cells correspond to the natural IPC, also described a s type 2 precursor dendritic cells. We also demonstrated that cytokines of possible importance in the pathogenesis in SLE had effects on the IFN-a pro duction. Specifically, the IFN-alpha production was strongly increased by t he type I IFNs, IFN-alpha and -beta, but markedly inhibited by IL-10 and al so 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 detec ted in PBMC stimulated by apoptotic U937 cells and SLE IgG. These results m ay explain the cause of the ongoing IFN-a production in SLE patients and it s relation to the autoimmune process. (C) 2001 Academic Press.