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Peripheral T Cell Functions Correlate with the Severity of Chronic Obstructive Pulmonary Disease¹

Division of Pulmonary, Allergy and Critical Care, University of Pittsburgh Medical Center, Pittsburgh, PA 15213

Adaptive immune processes have been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). We hypothesized that peripheral T cell abnormalities may be present in afflicted patients. We tested this hypothesis by characterizing circulating T cells in COPD patients and correlated these findings with disease severity, smoking status, and use of inhaled glucocorticosteroids (ICS). Compared with normal controls, a lesser proportion of peripheral CD4 T cells from COPD subjects produced IL-10, whereas the CD8 T cells from these patients were more often activated and more frequently produced both IFN- and IL-4. COPD severity was significantly and inversely associated with the proportion of circulating CD4 T cells and directly correlated with CD4 production of IL-2, as well as frequency of CD8 T cell activation and CD8 IFN- production. Adjustments for current smoking status and ICS use by linear regression showed independent, and generally inhibitory, effects of these clinical variables on the abnormal T cell functions of these patients. We conclude that circulating T cells from COPD patients are abnormally activated and elaborate proinflammatory mediators with admixed features of Th1 and Th2 responses. Furthermore, many of these effector processes are significantly correlated with disease severity. These findings further implicate adaptive immune processes in COPD progression and indicate that facile assays of peripheral lymphocytes may provide useful insights into disease mechanisms. Current smoking and ICS use had independent effects on T cell functions among the COPD subjects, illustrating the importance of controlling for clinical parameters as covariates in immunological studies of patients afflicted with this disease.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This research was supported in part by National Institutes of Health Grants 1R01HL073241 and 1 P50 HL084948.

² Current address: Laboratory of Organ Transplantation, Tongji Hospital, Huazhong University of Science and Technology, Wuhan, China 430030

³ Address correspondence and reprint requests to Dr. Steven R. Duncan, Pulmonary, Allergy, and Critical Care Medicine, 628 Northwest Montefiore University Hospital, 3459 Fifth Avenue, University of Pittsburgh, PA 15213. E-mail address: duncsr{at}upmc.edu

⁴ Abbreviations used in this paper: COPD, chronic obstructive pulmonary disease; ICS, inhaled glucocorticosteroid; GOLD, Global Initiative for Obstructive Lung Disease; FEV₁%p, forced expiratory volume in 1 s, as a percent of predicted values.