Peripheral Tc17 and Tc17/Interferon-γ Cells are Increased and Associated with Lung Function in Patients with Chronic Obstructive Pulmonary Disease.

BACKGROUND Chronic obstructive pulmonary disease (COPD) is characterized by progressive loss of lung function and local and systemic inflammation, in which CD8+ T-cells are believed to play a key role. Activated CD8+ T-cells differentiate into distinct subpopulations, including interferon-γ (IFN-γ)-producing Tc1 and interleukin (IL)-17-producing Tc17 cells. Recent evidence indicates that Tc17 cells exhibit considerable plasticity and may convert into IL-17/IFN-γ-double producing (Tc17/IFN-γ) cells when driven by inflammatory conditions. The aim of this study was to investigate the Tc17/IFN-γ subpopulation in peripheral blood of patients with COPD and to evaluate their potential roles in this disease. METHODS Peripheral blood samples were collected from 15 never-smokers, 23 smokers with normal lung function, and 25 patients with COPD (Global Initiative for Chronic Obstructive Lung Disease 2-4). Proportions of the IL-17/IFN-γ-double expressing subpopulation were assessed using flow cytometry. Plasma concentrations of cytokines favoring Tc17/IFN-γ differentiation were measured by enzyme-linked immunosorbent assay. RESULTS Patients with COPD had higher proportions of Tc17 cells and Tc17/IFN-γ cells in the peripheral blood than smokers and never-smokers. The plasticity of Tc17 cells was higher than that of Th17 cells. The percentages of Tc17 cells and Tc17/IFN-γ cells showed negative correlations with forced expiratory volume in 1 s % predicted value (r = -0.418, P = 0.03; r = -0.596, P = 0.002, respectively). The plasma concentrations of IL-6, transforming growth factor-β1, and IL-12 were significantly higher in patients with COPD compared with smokers and never-smokers. CONCLUSIONS Peripheral Tc17 cells are increased and more likely to convert to Tc17/IFN-γ cells in COPD, suggesting that Tc17 cell plasticity may be involved in persistent inflammation of the disease.