In vitro cytokine production and proliferation of T cells from patients with anti-proteinase 3- and antimyeloperoxidase-associated vasculitis, in response to proteinase 3 and myeloperoxidase

Arthritis Rheum. 2002 Jul;46(7):1894-904. doi: 10.1002/art.10384.


Objective: To investigate in vitro proliferative responses of CD4+ T cells and generation of specific cytokines induced by stimulation of peripheral blood mononuclear cells (PBMCs) from patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis with the autoantigens proteinase 3 (PR3) and myeloperoxidase (MPO).

Methods: PBMCs from vasculitis patients with PR3 ANCA or MPO ANCA and from healthy controls were stimulated for 7 days with PR3, MPO, or control stimuli. Proliferation of CD4+ T cells was assessed by flow cytometry, using the proliferation marker Ki-67. Levels of the pro-proliferative cytokines interleukin-2 (IL-2) and IL-6 and of the Th1 and Th2 cytokines interferon-gamma (IFN gamma) and IL-10 in culture supernatants were determined.

Results: PR3 and MPO induced proliferative responses in CD4+ T cells from individual patients with ANCA-associated vasculitides and healthy controls in vitro. Neither PR3 nor MPO elicited significant IL-2 production. Levels of IL-6 were highest after stimulation with PR3 but low after stimulation with MPO, independent of study group. Stimulation with PR3, and to a lesser extent with MPO, induced a Th2 cytokine milieu, characterized by high production of IL-6 and IL-10 and low production of IFN gamma in patients and controls.

Conclusion: PR3 and MPO promote proliferation of CD4+ T cells from patients with ANCA-associated vasculitides, but also cross-stimulate T cells from healthy individuals. Strong IL-10 production elicited by PR3 in vitro may act as an inhibitory signal for T cell proliferation and may have an important immunoregulatory function in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibodies, Antineutrophil Cytoplasmic / immunology
  • Autoantigens / immunology
  • Basic Helix-Loop-Helix Transcription Factors
  • CD4-Positive T-Lymphocytes / cytology*
  • Cell Division / drug effects*
  • Cytokines / biosynthesis*
  • DNA-Binding Proteins / biosynthesis
  • Female
  • Humans
  • In Vitro Techniques
  • Interferon-gamma / biosynthesis
  • Interleukin-10 / biosynthesis
  • Interleukin-2 / biosynthesis
  • Interleukin-6 / biosynthesis
  • Male
  • Middle Aged
  • Myeloblastin
  • Peroxidase / immunology*
  • Serine Endopeptidases / immunology*
  • Transcription Factors / biosynthesis
  • Vasculitis, Leukocytoclastic, Cutaneous / immunology*
  • Vasculitis, Leukocytoclastic, Cutaneous / metabolism
  • Vasculitis, Leukocytoclastic, Cutaneous / pathology


  • Antibodies, Antineutrophil Cytoplasmic
  • Autoantigens
  • Basic Helix-Loop-Helix Transcription Factors
  • Cytokines
  • DNA-Binding Proteins
  • Hand1 protein, mouse
  • Interleukin-2
  • Interleukin-6
  • Transcription Factors
  • Interleukin-10
  • Interferon-gamma
  • Peroxidase
  • Serine Endopeptidases
  • Myeloblastin