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

Gregory T Motz, Bryan L Eppert, Scott C Wesselkamper, Jennifer L Flury, Michael T Borchers
American Journal of Respiratory and Critical Care Medicine 2010 June 1, 181 (11): 1223-33

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.

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