1: Arthritis Rheum. 2002 Jul;46(7):1894-904. 

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.

Popa ER, Franssen CF, Limburg PC, Huitema MG, Kallenberg CG, Tervaert JW.

Department of Clinical Immunology, University Hospital Groningen, Groningen, The
Netherlands. E.Popa@med.rug.nl

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.

PMID: 12124874 [PubMed - indexed for MEDLINE]


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