Barczyk Adam, Pierzchała Władysław, Kon Onn M, Cosio Borja, Adcock Ian M, Barnes Peter J
Airways Disease Section, National Heart and Lung Institute, Imperial College, London, UK.
J Allergy Clin Immunol. 2006 Jun;117(6):1484-92. doi: 10.1016/j.jaci.2006.02.013. Epub 2006 Apr 3.
T lymphocytes (predominantly CD8+ cells) have previously been implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD).
We sought to describe the profile of cytokine production by CD8+ and CD4+ cells isolated from bronchoalveolar lavage fluid.
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.
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.
Our results suggest that there are increased numbers of TC2-like cytokine-expressing cells in the lungs of patients with COPD.
These cells might be a source of TH2 cytokines, which might, at least in part, explain the lung eosinophilia associated with COPD exacerbations.
T淋巴细胞（主要是CD8+细胞）先前被认为与慢性阻塞性肺疾病（COPD）的发病机制有关。
我们试图描述从支气管肺泡灌洗液中分离出的CD8+和CD4+细胞产生细胞因子的情况。
对11例慢性阻塞性肺疾病患者（FEV1中位数为预测值的63.3%）和9名健康对照者进行支气管肺泡灌洗。巨噬细胞清除后，通过阳性选择分离出CD8+和CD4+ T细胞。在用佛波醇12-肉豆蔻酸酯13-乙酸酯-离子霉素和布雷菲德菌素再次刺激前，用抗CD3/CD28抗体激活CD8+和CD4+细胞60小时。采用三色流式细胞术同时检测细胞内细胞因子水平。
与慢性阻塞性肺疾病患者的CD4+ T细胞（TH2）相比，刺激后的CD8+ T细胞（TC2）中IL-4表达的百分比更高（P = 0.01）。相比之下，在慢性阻塞性肺疾病组中，刺激后的CD4+ T细胞（TH1）中IFN-γ表达的百分比明显高于CD8+ T细胞（TC1）（P = 0.04）。几乎所有的TC1和TH1细胞都表达TNF-α，而TC2和TH2细胞几乎不表达。此外，在大多数受试者中，发现少数T细胞仅表达TNF-α，而不伴随IFN-γ或IL-4表达。与对照组相比，慢性阻塞性肺疾病患者中TC2细胞的百分比更高（P = 0.03）。用抗CD3/CD28抗体刺激可增加TC2细胞的百分比，降低TH2细胞的百分比。
我们的结果表明，慢性阻塞性肺疾病患者肺中表达细胞因子的TC2样细胞数量增加。
这些细胞可能是TH2细胞因子的来源，这可能至少部分解释了与慢性阻塞性肺疾病加重相关的肺嗜酸性粒细胞增多。
