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Smoking may induce changes in T lymphocyte cell subsets in peripheral blood. Abnormality of T lymphocyte cell subsets in peripheral blood and in bronchoalveolar-lavage fluid, and increased CD8+ T lymphocytes in the airways have been reported in patients with COPD. These findings suggest that T lymphocyte abnormalities might play a role in the pathogenesis of airflow limitation in smokers. To investigate this hypothesis this study was performed. Peripheral blood T lymphocyte cell subsets were measured by flow cytometry using specific monoclonal antibodies in 20 healthy nonsmokers, 20 healthy smokers, and 20 smokers with stable COPD. No significant differences in the peripheral blood T lymphocyte cell subsets were observed between the three groups. Because a previous study had shown peripheral blood T lymphocyte abnormalities in the subgroup of nonsmoking COPD subjects, we wanted to investigate what factors determine the subgroup of COPD with abnormal T lymphocyte cell subsets. We tried to measure the relationship between T lymphocyte cell subsets and physiologic indices of pulmonary function tests in smokers with COPD. The proportion of CD8+ T lymphocytes significantly correlated with DLco (p= 0.012) and DLco/VA (p=0.002), and CD4+/CD8+ ratio correlated with DLco/VA (p=0.01). Therefore, we attempted to divide the smokers with COPD into two subgroups on the basis of DLco/VA. Ten patients with low DLco/VA (DLco/VA<80 per cent predicted; COPD/low DLco/VA) and 10 patients with normal DLco/VA (DLco/VA≥80 per cent, COPD/normal DLco/VA) were subclassified. The COPD/normal DLco/VA subgroup had a significantly higher proportion of CD8+ T lymphocytes (p<0.5) and lower CD4+/CD8+ ratio (p<0.05) than the healthy smokers or COPD/low DLco/VA subgroup. Moreover,. FEV1/FVC significantly correlated with the CD4+/CD8+ ratio only in the COPD/normal DLco/VA subgroup (p=0.044). These findings suggest that T lymphocyte abnormalities might be involved in the pathogenesis of airflow limitation in a subgroup of COPE patients, presumably with small airways disease, but not in all COPD.