COPD Research Group, The School of Molecular Medical Sciences, The University of Nottingham, Nottingham, Nottinghamshire, United Kingdom.
PLoS One. 2013;8(3):e58556. doi: 10.1371/journal.pone.0058556. Epub 2013 Mar 11.
CD8(+) T-lymphocytes, natural killer T-like cells (NKT-like cells, CD56(+)CD3(+)) and natural killer cells (NK cells, CD56(+)CD3(-)) are the three main classes of human killer cells and they are implicated in the pathogenesis of chronic obstructive pulmonary disease (COPD). Activation of these cells can initiate immune responses by virtue of their production of inflammatory cytokines and chemokines that cause lung tissue damage, mucus hypersecretion and emphysema. The objective of the current study was to investigate the activation levels of human killer cells in healthy non-smokers, healthy smokers, ex-smokers with COPD and current smokers with COPD, in both peripheral blood and induced sputum.
METHODS/PRINCIPAL FINDINGS: After informed consent, 124 participants were recruited into the study and peripheral blood or induced sputum was taken. The activation states and receptor expression of killer cells were measured by flow cytometry. In peripheral blood, current smokers, regardless of disease state, have the highest proportion of activated CD8(+) T-lymphocytes, NKT-like cells and NK cells compared with ex-smokers with COPD and healthy non-smokers. Furthermore, CD8(+) T-lymphocyte and NK cell activation is positively correlated with the number of cigarettes currently smoked. Conversely, in induced sputum, the proportion of activated killer cells was related to disease state rather than current smoking status, with current and ex-smokers with COPD having significantly higher rates of activation than healthy smokers and healthy non-smokers.
A differential effect in systemic and lung activation of killer cells in COPD is evident. Systemic activation appears to be related to current smoking whereas lung activation is related to the presence or absence of COPD, irrespective of current smoking status. These findings suggest that modulating killer cell activation may be a new target for the treatment of COPD.
CD8(+)T 淋巴细胞、自然杀伤 T 样细胞（NKT 样细胞，CD56(+)CD3(+)）和自然杀伤细胞（NK 细胞，CD56(+)CD3(-)）是人类三种主要的杀伤细胞，它们与慢性阻塞性肺疾病（COPD）的发病机制有关。这些细胞的激活可以通过其产生的炎症细胞因子和趋化因子来启动免疫反应，从而导致肺组织损伤、黏液过度分泌和肺气肿。本研究的目的是研究健康非吸烟者、健康吸烟者、COPD 患者的既往吸烟者和 COPD 患者的现吸烟者外周血和诱导痰中人类杀伤细胞的激活水平。
方法/主要发现：在获得知情同意后，招募了 124 名参与者进行研究，并采集外周血或诱导痰。通过流式细胞术测量杀伤细胞的激活状态和受体表达。在外周血中，与 COPD 患者的既往吸烟者和健康非吸烟者相比，无论疾病状态如何，现吸烟者中激活的 CD8(+)T 淋巴细胞、NKT 样细胞和 NK 细胞的比例最高。此外，CD8(+)T 淋巴细胞和 NK 细胞的激活与目前吸烟的支数呈正相关。相反，在诱导痰中，激活的杀伤细胞比例与疾病状态有关，而与目前的吸烟状态无关，COPD 患者的现吸烟者和既往吸烟者的激活率明显高于健康吸烟者和健康非吸烟者。
在 COPD 中，杀伤细胞在全身和肺部的激活存在明显的差异效应。全身激活似乎与当前吸烟有关，而肺部激活与 COPD 的存在与否有关，而与当前的吸烟状态无关。这些发现表明，调节杀伤细胞的激活可能是 COPD 治疗的一个新靶点。
