Jeffery P K
Lung Pathology Unit (Department of Gene Therapy), Imperial College School of Medicine, Royal Brompton Hospital, Sydney Street, London SW3 6NP, UK.
Novartis Found Symp. 2001;234:149-61; discussion 161-8.
Chronic obstructive pulmonary disease (COPD) is a cytotoxic T lymphocyte (CD8)- and macrophage (CD68)-predominant chronic inflammatory disorder of the conducting airways and alveoli. This is often associated with a neutrophilia, inflammation of small airways and destruction of tissue beyond the terminal bronchiolus, i.e. emphysema. In contrast, asthma is a helper T cell (CD4; type 2)-predominant chronic inflammatory disorder of the conducting airways in which there is T lymphocyte-derived gene expression for interleukin (IL)-4 and IL-5 but not interferon gamma. There is fragility of airway surface epithelium, thickening of the reticular basement membrane, bronchial vessel congestion and (when severe) an increase in the mass of bronchial smooth muscle. This is usually (but not always) associated with tissue and peripheral blood eosinophilia rather than a neutrophilia and there is exudative plugging of the airways. These differences of inflammatory profile, remodelling and lung function are seen when smokers with COPD are compared with non-smoking mild asthmatics. However there may be important similarities and overlap, particularly in more severe asthma when neutrophils predominate and in the older and or smoking asthmatic when reversibility of airflow is less obvious. We have recently demonstrated gene expression for IL-4 and IL-5 in and around the mucus-secreting glands of airways resected from smokers without a history of asthma. Also exacerbations of bronchitis may be associated with a tissue eosinophilia. On examination of bronchial biopsies from these patients we show surprisingly strong gene expression for IL-4, IL-5 and even human eotaxin and RANTES (regulated on activation normal T cell expressed and secreted). Whilst CD4 T lymphocytes of the Th2 phenotype might be expressing these cytokines in bronchitis, CD8 T lymphocytes are also capable of secreting IL-4 and IL-5. Viruses may modulate these changes in distinct lymphocyte functional phenotypes. The relevance and importance of CD4/CD8 T lymphocyte ratio to the development of COPD is discussed.
慢性阻塞性肺疾病（COPD）是一种以细胞毒性T淋巴细胞（CD8）和巨噬细胞（CD68）为主的传导气道和肺泡的慢性炎症性疾病。这通常与中性粒细胞增多、小气道炎症以及终末细支气管远端组织破坏（即肺气肿）有关。相比之下，哮喘是以辅助性T细胞（CD4；2型）为主的传导气道慢性炎症性疾病，其中存在T淋巴细胞衍生的白细胞介素（IL）-4和IL-5基因表达，但不存在干扰素γ基因表达。气道表面上皮脆弱，网状基底膜增厚，支气管血管充血，严重时支气管平滑肌质量增加。这通常（但并非总是）与组织和外周血嗜酸性粒细胞增多而非中性粒细胞增多有关，且气道存在渗出性阻塞。当将患有COPD的吸烟者与非吸烟轻度哮喘患者进行比较时，可以看到这些炎症特征、重塑和肺功能的差异。然而，可能存在重要的相似之处和重叠，特别是在中性粒细胞占主导的更严重哮喘中，以及在气流可逆性不太明显的老年和/或吸烟哮喘患者中。我们最近在没有哮喘病史的吸烟者切除的气道黏液分泌腺及其周围组织中证实了IL-4和IL-5的基因表达。此外，支气管炎的加重可能与组织嗜酸性粒细胞增多有关。在检查这些患者的支气管活检样本时，我们发现IL-4、IL-5甚至人嗜酸性粒细胞趋化因子和调节激活正常T细胞表达和分泌的RANTES（regulated on activation normal T cell expressed and secreted）的基因表达异常强烈。虽然Th2表型的CD4 T淋巴细胞可能在支气管炎中表达这些细胞因子，但CD8 T淋巴细胞也能够分泌IL-4和IL-5。病毒可能会调节这些不同淋巴细胞功能表型的变化。本文讨论了CD4/CD8 T淋巴细胞比率与COPD发生发展的相关性和重要性。
