Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0056, USA.
Am J Respir Crit Care Med. 2010 Jun 1;181(11):1223-33. doi: 10.1164/rccm.200910-1485OC. Epub 2010 Feb 4.
Pathogenic T cells drive, or sustain, a number of inflammatory diseases. Chronic obstructive pulmonary disease (COPD) is an inflammatory lung disease associated with the accumulation of activated T cells. We previously demonstrated that chronic cigarette smoke (CS) exposure causes oligoclonal expansion of lung CD4(+) T cells and CD8(+) T cells in a mouse model of COPD, thus implicating these cells in disease pathogenesis.
To determine whether T cells are pathogenic in a CS-induced mouse model of COPD.
We transferred lung CD3(+) T cells from filtered air (FA)- and CS-exposed mice into Rag2(-/-) recipients. Endpoints associated with the COPD phenotype were then measured.
Here, we demonstrate that chronic CS exposure generates pathogenic T cells. Transfer of CD3(+) T cells from the lungs of CS-exposed mice into Rag2(-/-) recipients led to substantial pulmonary changes pathognomonic of COPD. These changes included monocyte/macrophage and neutrophil accumulation, increased expression of cytokines and chemokines, activation of proteases, apoptosis of alveolar epithelial cells, matrix degradation, and airspace enlargement reminiscent of emphysema.
These data formally demonstrate, for the first time, that chronic CS exposure leads to the generation of pathogenic T cells capable of inducing COPD-like disease in Rag2(-/-) mice. This report provides novel insights into COPD pathogenesis.
致病性 T 细胞驱动或维持着许多炎症性疾病。慢性阻塞性肺疾病（COPD）是一种与激活的 T 细胞积累相关的炎症性肺部疾病。我们之前的研究表明，慢性香烟烟雾（CS）暴露会导致 COPD 小鼠模型中肺 CD4(+)T 细胞和 CD8(+)T 细胞的寡克隆扩增，从而提示这些细胞参与了疾病的发病机制。
确定 T 细胞在 CS 诱导的 COPD 小鼠模型中是否具有致病性。
我们将来自过滤空气（FA）和 CS 暴露小鼠的肺 CD3(+)T 细胞转移到 Rag2(-/-)受体中。然后测量与 COPD 表型相关的终点。
我们证明慢性 CS 暴露会产生致病性 T 细胞。将来自 CS 暴露小鼠肺部的 CD3(+)T 细胞转移到 Rag2(-/-)受体中，会导致 COPD 的肺部变化。这些变化包括单核细胞/巨噬细胞和中性粒细胞的积累、细胞因子和趋化因子表达增加、蛋白酶激活、肺泡上皮细胞凋亡、基质降解和肺气肿样的气腔扩大。
这些数据首次正式证明，慢性 CS 暴露会导致产生能够在 Rag2(-/-)小鼠中诱导 COPD 样疾病的致病性 T 细胞。本报告为 COPD 的发病机制提供了新的见解。
