T-cells in COPD to help or harm? A study of T-cells in COPD patients and related aspects of T-cell function in vitro

Chronic obstructive pulmonary disease, COPD, is manifested by chronic airflow limitation due to inflammation and tissue destruction in the lungs. COPD is caused primarily by smoking and with increasing cigarette consumption in the world, the prevalence for COPD will most probably increase in the future. The chronic inflammation in the lungs of these patients is thought to drive the pathogenesis forward. Neutrophils, macrophages, T-cells and epithelial cells are considered major players in the inflammation. This thesis focuses on T-cells and the occurrence of T-cell populations in BAL, blood and peripheral lung tissue from COPD patients. In addition, T-cell responses to smoke and costimulatory factors were studied in vitro. In the papers covered in this thesis we show that T-cells in BAL displayed a memory phenotype (CD45R0+) and the majority of the cells also expressed the integrin alphaEbeta7, which implies that these cells have previously been situated in the airway epithelium as intraepithelial T-cells. In vitro studies of T-cells from peripheral blood, negative for alphaEbeta7, showed that expression of alphaEbeta7 was increased after exposure to TGF-beta and stimulation of T-cells via LFA-1. In peripheral lung tissue CD4+ and CD8+ T-cells were located at different sites. CD8+ T-cells were more abundant in the epithelium and CD4+T-cells were numerous in lymphoid aggregates found in the parenchyma. The number of lymphoid aggregates found per cm2 tissue tended to be higher in COPD patients than in smokers and never-smokers and constituted of a B-cell core surrounded by T-cells of mainly CD4+ phenotype. In blood the number of CD4+ T-cells was elevated in smokers and CD69 expression on CD4+ T-cells in current smokers correlated with FEV1 percent of predicted, which suggests that high numbers of CD69+CD4+ T-cells in blood of smokers could protect against lung function deterioration while exposure of cigarette smoke is present. Despite high numbers of T-cells present in the lungs of smokers and COPD patients, the lower airways of these patients are often colonized by bacteria. In the present study T-cells exposed to an aqueous cigarette smoke extract were studied with the hypothesis that T-cell functions may be impaired in response to substances in cigarette smoke. Indeed, T-cell activation, proliferation and production of cytotoxic granules were decreased in response to cigarette smoke extract. These data suggest that T-cell defence against airway infections might be impaired in smokers