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 rspiratory tract, lung, and kidney. Slice 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. PBMs wer isolated from 12 patients with active WG, 7 patients with inactive disease, and 12 healthy normal donors. PBMs from clinically active WG patients exhibited increased proliferation following stimulation with either PMA/lonomycin or anti-CD2 and anti-CD28, when compard with normal donors. In addition, these PBMCs exhibited increased secretion of IFN-γ, but not of IL-4, IL-5, or IL-10. Furthermore, TNF-α production from PBMCs and CD4⁺ T cells isolated from patients with WG was elevated, when compard 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-γ 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-γ and TNF-α, probably due to dysregulated IL-12 secretion, and that IL-10 may therefor have therapeutic implications for this disease.