Peripheral T cell functions correlate with the severity of chronic obstructive pulmonary disease.

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-gamma 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-gamma 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.

Autoantibodies in patients with chronic obstructive pulmonary disease.

RATIONALE: Adaptive immune responses are present in patients with chronic obstructive pulmonary disease (COPD), and it has been postulated that these processes could be autoreactive. OBJECTIVES: To ascertain if humoral autoimmunity could play a role in COPD pathogenesis. METHODS: Circulating IgG autoantibodies were detected by immunofluorescence and immunoprecipitation. Immunohistochemistry and immunofluorescence were used to evaluate intrapulmonary IgG and complement (C3) deposition in human lung explants. Autoantibody pathogenicity was also investigated with an antibody-dependent cell-mediated cytotoxicity assay. MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HEp-2 epithelial cell autoantibodies in 47 smokers/former smokers with COPD (GOLD stages 1-4) was greater than among 8 subjects with a smoking history but normal spirometry and 21 healthy control subjects who had never smoked (68 vs. 13 vs. 10%, respectively; P < 0.0001). Antibodies against primary pulmonary epithelial cells were found in 12 of 12 patients with COPD versus 3 of 12 never-smoked control subjects (P < 0.001). Self-antigens immunoprecipitated from 34 of 35 (97%) of COPD plasmas (vs. 0/12 never-smoked controls). Antibodies against a particular 130-kD autoantigen (n = 7) were associated with decreased body mass index (23.2 +/- 2.1 vs. 29.5 +/- 1.0 kg/m(2), P = 0.007). Intrapulmonary immune complexes were present in six of six and C3 was seen in five of six COPD lung explants, unlike zero of six and one of six normals, respectively. Cytotoxicity of pulmonary epithelial cells by allogeneic mononuclear cells also increased 46% after incubation with COPD plasmas (n = 10), compared with identical treatments with eight normal specimens (P = 0.03). CONCLUSIONS: IgG autoantibodies with avidity for pulmonary epithelium, and the potential to mediate cytotoxicity, are prevalent in patients with COPD. Autoreactive adaptive immune responses may be important in the etiology of this disease.