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.

Abstract

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.

• Authors: E R Popa, C F M Franssen, P C Limburg, M G Huitema, C G M Kallenberg, J W Cohen Tervaert
• Journal: Arthritis and rheumatism (Arthritis Rheum) Vol. 46 Issue 7 Pg. 1894-904 (Jul 2002) ISSN: 0004-3591 [Print] United States
• PMID: 12124874 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• 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, metabolism, pathology)