Chronic Cigarette Smoke Exposure Generates Pathogenic T Cells Capable of Driving COPD-like Disease in Rag2−/− Mice
GT Motz, BL Eppert, SC Wesselkamper… - American journal of …, 2010 - atsjournals.org
GT Motz, BL Eppert, SC Wesselkamper, JL Flury, MT Borchers
American journal of respiratory and critical care medicine, 2010•atsjournals.orgRationale: 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 …
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 …
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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