Phenotypic characterisation of T-lymphocytes in COPD: abnormal CD4+CD25+ regulatory T-lymphocyte response to tobacco...

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.