Active Wegener's Granulomatosis Is Associated with HLA-DR+ CD4+ T Cells Exhibiting an Unbalanced Th1-Type T Cell Cytokine Pattern: Reversal with IL-10

Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the upper respiratory tract, lung, and kidney. Since T cells make up a significant proportion of cells infiltrating granulomatous lesions in WG, we investigated the proliferative response and cytokine profile of T cells fr...

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Bibliographic Details
Published in:The Journal of immunology (1950) 1998-04, Vol.160 (7), p.3602-3609
Main Authors: Ludviksson, Bjorn R, Sneller, Michael C, Chua, Kevin S, Talar-Williams, Cheryl, Langford, Carol A, Ehrhardt, Rolf O, Fauci, Anthony S, Strober, Warren
Format: Article
Language:English
Subjects:
Adult
AIDS/HIV
CD4 Antigens - analysis
Cells, Cultured
Cytokines - antagonists & inhibitors
Cytokines - blood
Cytokines - secretion
Female
Granulomatosis with Polyangiitis - immunology
HLA-DR Antigens - analysis
Humans
Interferon-gamma - antagonists & inhibitors
Interleukin-10 - pharmacology
Lymphocyte Activation
Male
Middle Aged
Monocytes - secretion
Th1 Cells - metabolism
Th1 Cells - secretion
Tumor Necrosis Factor-alpha - secretion
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Summary:Wegener's granulomatosis (WG) is a granulomatous vasculitis that affects the upper respiratory tract, lung, and kidney. Since T cells make up a significant proportion of cells infiltrating granulomatous lesions in WG, we investigated the proliferative response and cytokine profile of T cells from these patients. PBMCs were isolated from 12 patients with active WG, 7 patients with inactive disease, and 12 healthy normal donors. PBMCs from clinically active WG patients exhibited increased proliferation following stimulation with either PMA/ionomycin or anti-CD2 and anti-CD28, when compared with normal donors. In addition, these PBMCs exhibited increased secretion of IFN-gamma, but not of IL-4, IL-5, or IL-10. Furthermore, TNF-alpha production from PBMCs and CD4+ T cells isolated from patients with WG was elevated, when compared with healthy donors. In further studies, we investigated the ability of WG patients' monocytes to produce IL-12 and showed that both inactive and active patients produced increased amounts of IL-12. Finally, the in vitro IFN-gamma production by WG PBMC is inhibited in a dose-dependent manner by exogenous IL-10. These data suggest that T cells from WG patients overproduce IFN-gamma and TNF-alpha, probably due to dysregulated IL-12 secretion, and that IL-10 may therefore have therapeutic implications for this disease.
ISSN:0022-1767
1550-6606
DOI:10.4049/jimmunol.160.7.3602