Bronchoalveolar Lavage Fluid IFN-γ+ Th17 Cells and Regulatory T Cells in Pulmonary Sarcoidosis

In sarcoidosis, increased Th17 cell fractions have been reported in bronchoalveolar lavage fluid, and elevated numbers of Th17 cells producing IFN-gamma have been observed in peripheral blood. The balance between Th1, Th17, and FoxP3(+) CD4(+) T cell subsets in sarcoidosis remains unclear. Bronchoalveolar lavage fluid cells, from 30 patients with sarcoidosis, 18 patients with other diffuse parenchymal lung diseases, and 15 healthy controls, were investigated with flow cytometry for intracellular expression of FoxP3. In a subset of the patients, expression of the cytokines IL17A and IFN-gamma was investigated. The fractions of FoxP3(+) CD4(+) T cells and Th17 cells were both lower in sarcoidosis compared to controls (P = 0.017 and P = 0.011, resp.). The proportion of Th17 cells positive for IFN-gamma was greater in sarcoidosis than controls (median 72.4% versus 31%, P = 0.0005) and increased with radiologic stage (N = 23, rho = 0.45, and P = 0.03). IFN-gamma(+) Th17 cells were highly correlated with Th1 cells (N = 23, rho = 0.64, and.. = 0.001), and the ratio of IFN-gamma(+) Th17/FoxP3(+) CD4(+) T cells was prominently increased in sarcoidosis. IFN-gamma(+) Th17 cells may represent a pathogenic subset of Th17 cells, yet their expression of IFN-gamma could be a consequence of aTh1-polarized cytokine milieu. Our results indicate a possible immune cell imbalance in sarcoidosis.