Cytokine production by bronchoalveolar lavage T lymphocytes in chronic obstructive pulmonary disease

Background: T lymphocytes (predominantly CD8(+) cells) have previously been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Objective: We sought to describe the profile of cytokine production by CD8(+) and CD4(+) cells isolated from bronchoalveolar lavage fluid. Methods: Bronchoalveolar lavage was performed in 11 patients with COPD (median FEV1, 63.3% of predicted value) and 9 healthy control subjects. CD8(+) and CD4+ T cells were isolated by means of positive selection after macrophage depletion. CD8(+) and CD4(+) cells were activated with anti-CD3/CD28 antibodies for 60 hours before restimulation with phorbol 12-myristate 13-acetate-ionomycin and brefeldin. Three-color How cytometry was used to simultaneously measure levels of intracellular cytokines. Results: IL-4 was expressed by a higher percentage of stimulated CD8(+) T cells (T(C)2) compared with CD4(+) T cells (T(H)2) in patients with COPD (P = .01). In contrast, IFN-gamma was expressed in a significantly higher percentage of stimulated CD4(+) T cells (T(H)1) than CD8(+) T cells (T(C)1) in the COPD group (P = .04). TNF-alpha was expressed by almost all T(C)1 and T(H)1 cells, with virtually no expression by T(C)2 and TH2 cells. In addition, a small number of T cells expressing TNF-alpha: alone without concomitant IFN-gamma or IL-4 expression were seen in the majority of subjects. There was a higher percentage of T(C)2 cells in subjects with COPD compared with that seen in the control group (P = .03). Stimulation with anti-CD3/CD28 antibodies increased the percentage of T(C)2 cells and decreased the percentage of T(H)2 cells. Conclusion: Our results suggest that there are increased numbers of T(C)2-like cytokine-expressing cells in the lungs of patients with COPD. Clinical implications: These cells might be a source of T(H)2 cytokines, which might, at least in part, explain the lung eosinophilia associated with COPD exacerbations.