Division of Pulmonary Allergy and Critical Care Medicine, University of Texas Medical Branch, 301 University Blvd., Galveston, TX 77555-0561, USA.
Proc Am Thorac Soc. 2009 Dec 1;6(7):573-80. doi: 10.1513/pats.200904-022RM.
Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the lungs that usually manifests late in life. Physiologic and immunologic changes that occur in COPD often mimic changes seen in the aging lung. This has led some to characterize COPD as an "accelerated aging phenotype." At the molecular level, COPD and aging share common mechanisms and are associated with significant dysregulation of the immune systems. Aging and COPD are characterized by increases in proinflammatory cytokines such as interleukin (IL)-6 and tumor necrosis factor (TNF)-alpha, which are implicated in aging-related inflammatory diseases and correlate with degree of obstruction in COPD. There is an age-dependent decline in naïve T cells with oligoclonal expansion of CD8(+) CD28(null) T cells from chronic antigenic stimulation. The increase in CD8(+) CD28 (null) T regulatory cells inhibits antigen-specific CD4(+) T cell responses, leading to a decline in adaptive immune response. To compensate for the decline in the adaptive immune function there is a paradoxical up-regulation of innate immune system resulting in a proinflammatory state. The dysregulated adaptive immune system with activated innate immune responses seen with aging results in recruitment and retention of neutrophils, macrophages, and CD4(+) and CD8(+) T cells in the lungs of smokers with COPD. Once the inflammation is triggered, there is a self-perpetuating cascade of inflammation and lung parenchymal damage. This review will focus on how the aging immune system may contribute to COPD development later in life in susceptible individuals.
慢性阻塞性肺疾病（COPD）是一种慢性肺部炎症性疾病，通常在生命后期出现。COPD 中发生的生理和免疫变化通常类似于衰老肺部的变化。这导致一些人将 COPD 描述为一种“加速衰老表型”。在分子水平上，COPD 和衰老具有共同的机制，并与免疫系统的显著失调有关。衰老和 COPD 的特征是促炎细胞因子（如白细胞介素 [IL]-6 和肿瘤坏死因子 [TNF]-alpha）的增加，这些细胞因子与与衰老相关的炎症性疾病有关，并与 COPD 的阻塞程度相关。随着年龄的增长，幼稚 T 细胞数量减少，而慢性抗原刺激导致 CD8(+) CD28(null)T 细胞的寡克隆扩增。CD8(+) CD28(null)T 调节细胞的增加抑制了抗原特异性 CD4(+)T 细胞反应，导致适应性免疫反应下降。为了弥补适应性免疫功能的下降，先天免疫系统出现反常的上调，导致炎症状态。衰老时适应性免疫系统失调和先天免疫反应激活导致 COPD 吸烟者肺部中性粒细胞、巨噬细胞以及 CD4(+)和 CD8(+)T 细胞的募集和保留。一旦炎症被触发，就会出现炎症和肺实质损伤的自我维持级联反应。这篇综述将重点讨论衰老的免疫系统如何在易感个体中导致 COPD 在生命后期的发展。
