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

摘要

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 Tc 1 and interleukin (IL)-17-producing Tc 1 7 cells.Recent evidence indicates that Tc 17 cells exhibit considerable plasticity and may convert into IL-17/IFN-γ-double producing (Tc1 7/IFN-γ) cells when driven by inflammatory conditions.The aim of this study was to investigate the Tc 17/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 Tc 17/IFN-γ differentiation were measured by enzymelinked 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 Tc 17 cells was higher than that of Th 17 cells.The percentages ofTc 17 cells and Tc 17/IFN-γcells 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.