Ontology highlight
ABSTRACT: Rationale
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.Objectives
To determine whether T cells are pathogenic in a CS-induced mouse model of COPD.Methods
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.Measurements and main results
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.Conclusions
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.
SUBMITTER: Motz GT
PROVIDER: S-EPMC2891493 | biostudies-literature | 2010 Jun
REPOSITORIES: biostudies-literature
American journal of respiratory and critical care medicine 20100204 11
<h4>Rationale</h4>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.<h4>Objectives</h4>To determine whether T cells are patho ...[more]