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*
Mucosal Immunity Section, Laboratory of Clinical Investigation, and
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892
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-
, but not of IL-4, IL-5, or IL-10. Furthermore, TNF-
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-
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- and TNF-, probably due to dysregulated IL-12
secretion, and that IL-10 may therefore have therapeutic implications
for this disease.
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