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 flow cytometry was used to simultaneously measure levels of intracellular cytokines. RESULTS: IL-4 was expressed by a higher percentage of stimulated CD8+ T cells (TC2) compared with CD4+ T cells (TH2) in patients with COPD (P = .01). In contrast, IFN-gamma was expressed in a significantly higher percentage of stimulated CD4+ T cells (TH1) than CD8+ T cells (TC1) in the COPD group (P = .04). TNF-alpha was expressed by almost all TC1 and TH1 cells, with virtually no expression by TC2 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 TC2 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 TC2 cells and decreased the percentage of TH2 cells. CONCLUSION: Our results suggest that there are increased numbers of TC2-like cytokine-expressing cells in the lungs of patients with COPD. CLINICAL IMPLICATIONS: These cells might be a source of TH2 cytokines, which might, at least in part, explain the lung eosinophilia associated with COPD exacerbations.
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 flow cytometry was used to simultaneously measure levels of intracellular cytokines. RESULTS:IL-4 was expressed by a higher percentage of stimulated CD8+ T cells (TC2) compared with CD4+ T cells (TH2) in patients with COPD (P = .01). In contrast, IFN-gamma was expressed in a significantly higher percentage of stimulated CD4+ T cells (TH1) than CD8+ T cells (TC1) in the COPD group (P = .04). TNF-alpha was expressed by almost all TC1 and TH1 cells, with virtually no expression by TC2 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 TC2 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 TC2 cells and decreased the percentage of TH2 cells. CONCLUSION: Our results suggest that there are increased numbers of TC2-like cytokine-expressing cells in the lungs of patients with COPD. CLINICAL IMPLICATIONS: These cells might be a source of TH2 cytokines, which might, at least in part, explain the lung eosinophilia associated with COPD exacerbations.
Authors: Timothy W Shipley; Heather M Kling; Alison Morris; Sangita Patil; Jan Kristoff; Siobhan E Guyach; Jessica E Murphy; Xiuping Shao; Frank C Sciurba; Robert M Rogers; Thomas Richards; Paul Thompson; Ronald C Montelaro; Harvey O Coxson; James C Hogg; Karen A Norris Journal: J Infect Dis Date: 2010-07-15 Impact factor: 5.226
Authors: Min-Jong Kang; Je-Min Choi; Bo Hye Kim; Chang-Min Lee; Won-Kyung Cho; Gina Choe; Do-Hyun Kim; Chun Geun Lee; Jack A Elias Journal: Am J Respir Crit Care Med Date: 2012-03-01 Impact factor: 21.405
Authors: Christine M Freeman; MeiLan K Han; Fernando J Martinez; Susan Murray; Lyrica X Liu; Stephen W Chensue; Timothy J Polak; Joanne Sonstein; Jill C Todt; Theresa M Ames; Douglas A Arenberg; Catherine A Meldrum; Christi Getty; Lisa McCloskey; Jeffrey L Curtis Journal: J Immunol Date: 2010-04-28 Impact factor: 5.422