Lung Dendritic Cell Expression of Maturation Molecules Increases with Worsening Chronic Obstructive Pulmonary Disease
Lung Dendritic Cell Expression of Maturation Molecules Increases with Worsening Chronic Obstructive Pulmonary Disease
复制标题
DOI：
10.1164/rccm.200904-0552oc
复制
发表时间：
2009-12-15
影响因子：
24.7
通讯作者：
Curtis, Jeffrey L.
中科院分区：
文献类型：
--
作者：
Freeman, Christine M.;Martinez, Fernando J.;Curtis, Jeffrey L.
基本原理 树突状细胞 (DC) 在慢性阻塞性肺疾病 (COPD) 中尚未得到充分研究，但它们在激活和分化 T 细胞中的不可或缺的作用使它们成为 COPD 发病机制的潜在参与者。 目的： 确定各个 DC 亚群成熟分子的表达与 COPD 阶段以及肺 CD4(+) T 细胞急性激活标记物 CD69 表达的关系。 方法： 我们以非酶促方式从人类手术标本中释放肺白细胞 (n = 42）并使用流式细胞术鉴定了三个 DC 子集（mDC1、mDC2 和 pDD），并测量了它们三种共刺激分子（CD40、CD80 和 CD86）以及 CD83（DC 成熟的决定性标志物）的表达。使用 Spearman 非参数相关分析来确定 DC 成熟分子的表达与 COPD 严重程度之间的显着相关性。测量和主要结果：无论 GOLD 阶段如何，mDC1 和 mDC2 的 CD40 表达以及 mDC2 的 CD86 表达都很高，但这两个 DC 亚群上的 CD80 和 CD83 随着疾病进展而增加。 pDC 还显示 CD40 和 CD80 表达显着增加。除一种随 COPD 严重程度增加而增加的 DC 分子的表达也与同一患者肺 CD4+ T 细胞上的 CD69 表达相关（mDC2 上的 CD83 除外）。 结论：这项横断面研究表明，COPD 进展与多个肺 DC 亚群共刺激分子表达的显着增加有关。与肺 DC 的相互作用可能有助于晚期 COPD 中 CD4(+) T 细胞的免疫表型。
Rationale Dendritic cells (DCs) have not been well studied in chronic obstructive pulmonary disease (COPD), yet their integral role in activating and differentiating T cells makes them potential participants in COPD pathogenesis.Objectives: To determine the expression of maturation molecules by individual DC subsets in relationship to COPD stage and to expression of the acute activation marker CD69 by lung CD4(+) T cells.Methods: We nonenzymatically released lung leukocytes from human surgical specimens (n = 42) and used flow cytometry to identify three DC subsets (mDC1, mDC2, and pDD) and to measure their expression of three costimulatory molecules (CD40, CD80 and CD86) and of CD83, the definitive marker of DC maturation. Spearman nonparametric correlation analysis was used to identify significant correlations between expression of DC maturation molecules and COPD severity.Measurements and Main Results: Expression of CD40 by mDC1 and mDC2 and of CD86 by mDC2 was high regardless of GOLD stage, but CD80 and CD83 on these two DC subsets increased with disease progression. pDC also showed significant increases in expression of CD40 and CD80. Expression of all but one of the DC molecules that increased with COPD severity also correlated with CD69 expression on lung CD4(+) T cells from the same patients, with the exception of CD83 on mDC2.Conclusions: This cross-sectional study implies that COPD progression is associated with significant increases in costimulatory molecule expression by multiple lung DC subsets. Interactions with lung DCs may contribute to the immunophenotype of CD4(+) T cells in advanced COPD.