Chemotactic Mediators of Th1 T-cell Trafficking in Smokers and COPD Patients

Abstract

Chronic obstructive pulmonary disease (COPD) is smoking-related and associated with increased cytotoxic CD8+ T-cells in the airway. There is a wide range of susceptibility to the damaging effects of cigarette smoke with only a small proportion of smokers progressing to COPD. We have previously reported increased intracellular Th1 cytokines in blood, BAL and intraepithelial CD8+T cells in current and ex-smokers with COPD, whereas healthy smokers showed localized Th1 response in the lung only. We thus hypothesised that Th1-associated chemokines or their receptors on CD8+T-cells may be differentially expressed in the blood of healthy smokers, current smoker COPD subjects and those who had ceased smoking. We investigated chemokines, chemokine receptors and Th1 and cytotoxic T-cell markers in blood and BAL using flow cytometry, ELISA and cytometric bead array. In blood, CXCR3, CCR4, intracellular CCR3 and the Th1 marker 62L⁻CD45RO⁺ were increased in both COPD groups and healthy smokers. In contrast, cytotoxic T-cells, ITAC, MIG, IFN-γ and CCR5 were increased in both COPD groups but not smokers. In BAL, the Th1 marker 62L⁻CD45RO⁺, CCR5, CXCR3, IFN-γ, RANTES, IL-8, MCP-1, MIG and ITAC were increased in both COPD groups and smokers versus controls. Our findings are consistent with systemic inflammation in COPD associated with an increased influx of cytotoxic and Th1 cells into the airway. The differential expression of specific chemokines and their receptors in blood from COPD subjects and healthy smokers suggests that inclusion of these markers in any panel designed for the non-invasive investigation of smokers with a disposition to COPD would be clinically relevant.