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

J Autoimmun. 2001 Aug;17(1):71-80. doi: 10.1006/jaut.2001.0519.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Aged
  • Apoptosis / immunology*
  • Autoantibodies / physiology*
  • Cells, Cultured
  • Cytokines / physiology*
  • Female
  • Flow Cytometry
  • Humans
  • Immunoglobulin G / physiology*
  • Immunophenotyping
  • Interferon-alpha / biosynthesis
  • Interferon-alpha / metabolism*
  • Interleukin-10 / biosynthesis
  • Leukocytes, Mononuclear / immunology
  • Leukocytes, Mononuclear / metabolism
  • Lupus Vulgaris / immunology*
  • Male
  • Scattering, Radiation
  • U937 Cells / cytology*
  • U937 Cells / immunology*
  • U937 Cells / metabolism
  • U937 Cells / radiation effects
  • Ultraviolet Rays


  • Autoantibodies
  • Cytokines
  • Immunoglobulin G
  • Interferon-alpha
  • Interleukin-10