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Am J Respir Crit Care Med. 2010 Jun 1;181(11):1223-33. doi: 10.1164/rccm.200910-1485OC. Epub 2010 Feb 4.

Chronic cigarette smoke exposure generates pathogenic T cells capable of driving COPD-like disease in Rag2-/- mice.

Author information

1
Department of Environmental Health, Division of Environmental Genetics and Molecular Toxicology, University of Cincinnati, College of Medicine, Cincinnati, OH 45267-0056, USA.

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.

PMID:
20133926
PMCID:
PMC2891493
DOI:
10.1164/rccm.200910-1485OC
[Indexed for MEDLINE]
Free PMC Article

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