Tobacco smoking induces an inflammatory response in the lungs of all smokers but, for reasons that are still poorly understood, only a proportion of them develop chronic obstructive pulmonary disease (COPD). Recent evidence indicates that this inflammatory response persists after smoking cessation, suggesting some type of auto-perpetuation mechanism similar to that described in autoimmune disorders. T-lymphocytes (CD4+ and CD8+) have been implicated in the pathogenesis of both COPD and several autoimmune processes. A subtype of regulatory CD4+ T-cells expressing CD25 (Tregs) plays a critical role in the maintenance of peripheral tolerance and the prevention of autoimmunity, but their potential role in COPD has not been explored. The present study sought to evaluate maturation (CD45RA/CD45R0) and activation markers (CD28) of T-lymphocytes and to explore potential Treg abnormalities in COPD.Flow cytometry was used to characterise T-lymphocytes obtained from blood and bronchoalveolar lavage fluid (BALF) in 23 patients with moderate COPD, 29 smokers with normal lung function and seven never-smokers.The main findings were that in BALF: patients with COPD showed higher CD8+CD45RA+ and lower CD8+CD45R0+ than smokers with normal lung function; and compared with never-smokers, smokers with preserved lung function showed a prominent upregulation of Tregs that was absent in patients with COPD.These observations indicate a final maturation-activation state of CD8+ T-lymphocytes in chronic obstructive pulmonary disease and, for the first time, identify a blunted regulatory T-cell response to tobacco smoking in these patients, further supporting a potential involvement of the acquired immune response in the pathogenesis of the disease.

Chronic obstructive pulmonary disease (COPD) is characterized by an excessive inflammatory response to inhaled particles, mainly tobacco smoking. T lymphocytes are important regulatory cells that secrete several cytokines and participate actively in this inflammatory response. According to the pattern of cytokines secreted, the immune response is classified as cytotoxic or type 1 [interferon (IFN)-γ-, interleukin (IL)-2-dependent] and humoral or type 2 (IL-4-, IL-5-, IL-10- and IL-13-dependent). This paper sought to compare the intracellular profile of cytokine expression determined by flow cytometry in T lymphocytes harvested from bronchoalveolar lavage (BAL) and peripheral blood in patients with COPD, smokers with normal lung function and never smokers. We found that BAL T lymphocytes from COPD patients had a higher percentage of positive stained cells for most of the cytokines analysed when compared to never smokers or smokers with normal lung function. Differences reached statistical significance for IL-4, IL-10 and IL-13, particularly in CD8⁺ T cells. Furthermore, the expression of most of these cytokines was related inversely to the degree of airflow obstruction present suggesting local activation and/or selective homing of T lymphocytes to the lungs in COPD patients. These observations were not reproduced in circulating T lymphocytes. These results suggest that BAL T lymphocytes in patients with COPD produce more cytokines than in controls and tend to show a type 2 pattern of intracellular cytokine expression, particularly a Tc-2 profile. This is related inversely to the degree of airflow obstruction present.

Chronic obstructive pulmonary disease (COPD) is characterised by an excessive inflammatory response to inhaled particles, mostly tobacco smoking. Although inflammation is present in all smokers, only a percentage of them develop COPD. T-lymphocytes are important effector and regulatory cells that participate actively in the inflammatory response of COPD. They comprise the T-cell receptor (TCR)-αβ (CD4+ and CD8+) and TCR-γδ T-lymphocytes. The latter represent a small percentage of the total T-cell population, but play a key role in tissue repair and mucosal homeostasis.To investigate TCR-αβ (CD4+ and CD8+) and TCR-γδ T-lymphocytes in COPD, the present authors determined, by flow cytometry, the distribution of both subpopulations in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from patients with COPD, smokers with normal lung function and never-smokers.The present study found that: 1) the distribution of CD4+ and CD8+ lymphocytes in blood and BAL was similar in all three groups; 2) compared with nonsmokers, γδ T-lymphocytes were significantly increased in smokers with preserved lung function; and 3) this response was blunted in patients with COPD.These results highlight a novel, potentially relevant, pathogenic mechanism in chronic obstructive pulmonary disease.

The present study tested the hypothesis that alveolar macrophages (AM) from patients with chronic obstructive pulmonary disease (COPD) release more pro-inflammatory and/or less anti-inflammatory mediators than those from smokers with normal lung function and never-smokers.AM were sorted by flow cytometry from bronchoalveolar lavage fluid in 13 patients with COPD (mean±SEM67±2 yrs, forced expiratory volume in one second (FEV₁) 61±4% reference), 16 smokers with normal lung function (55±2 yrs, FEV₁97±4% reference) and seven never-smokers (67±7 yrs, FEV₁94±4% reference). After sorting, AM were cultured (with and without lipopolysaccharide stimulation) after 4 h and 24 h, and the concentrations of leukotriene B₄(LTB₄), transforming growth factor (TGF)-β₁and tissue inhibitor of metalloproteinase (TIMP)-1 were quantified in the supernatant by ELISA. The production of reactive oxygen intermediates (ROI) in freshly isolated AM was determined by flow cytometry.LTB₄secretion and ROI production were not different between groups. In contrast, AM from COPD patients released significantly less TGF-β₁and TIMP-1 than those from smokers with normal lung function and nonsmokers.In conclusion, these observations are compatible with reduced anti-inflammatory and anti-elastolytic capacity in chronic obstructive pulmonary disease, which is likely to contribute to the pathogenesis of the disease.