Th17 and th1 T-cell responses in giant cell arteritis

Background—In giant cell arteritis (GCA), vasculitic damage of the aorta and its branches is combined with a syndrome of intense systemic inflammation. Therapeutically, glucocorticoids remain the gold standard because they promptly and effectively suppress acute manifestations; however, they fail to eradicate vessel wall infiltrates. The effects of glucocorticoids on the systemic and vascular components of GCA are not understood. Methods and Results—The immunoprofile of untreated and glucocorticoid-treated GCA was examined in peripheral blood and temporal artery biopsies with protein quantification assays, flow cytometry, quantitative real-time polymerase chain reaction, and immunohistochemistry. Plasma interferon- and interleukin (IL)-17 and frequencies of interferon-– producing and IL-17–producing T cells were markedly elevated before therapy. Glucocorticoid treatment suppressed the Th17 but not the Th1 arm in the blood and the vascular lesions. Analysis of monocytes/macrophages in the circulation and in temporal arteries revealed glucocorticoid-mediated suppression of Th17-promoting cytokines (IL-1, IL-6, and IL-23) but sparing of Th1-promoting cytokines (IL-12). In human artery–severe combined immunodeficiency mouse chimeras, in which patient-derived T cells cause inflammation of engrafted human temporal arteries, glucocorticoids were similarly selective in inhibiting Th17 cells and leaving Th1 cells unaffected. Conclusions—Two pathogenic pathways mediated by Th17 and Th1 cells contribute to the systemic and vascular manifestations of GCA. IL-17–producing Th17 cells are sensitive to glucocorticoid-mediated suppression, bu