Functional characterization of T cell populations in a mouse model of chronic obstructive pulmonary disease.

Cigarette smoke (CS) exposure is the primary risk factor for the development of chronic obstructive pulmonary disease (COPD). COPD is characterized by chronic peribronchial, perivascular, and alveolar inflammation. The inflammatory cells consist primarily of macrophage, neutrophils, and lymphocytes. Although myeloid cells are well studied, the role of lymphocyte populations in pathogenesis of COPD remains unclear. Using a mouse model of CS-induced emphysema, our laboratory has previously demonstrated that CS exposure causes changes in the TCR repertoire suggestive of an Ag-specific response and triggers a pathogenic T cell response sufficient to cause alveolar destruction and inflammation. We extend these findings to demonstrate that T cells from CS-exposed mice of the BALB/cJ or C57B6 strain are sufficient to transfer pulmonary pathology to CS-naive, immunosufficient mice. CS exposure causes a proinflammatory phenotype among pulmonary T cells consistent with those from COPD patients. We provide evidence that donor T cells from CS-exposed mice depend on Ag recognition to transfer alveolar destruction using MHC class I-deficient recipient mice. Neither CD4(+) nor CD8(+) T cells from donor mice exposed to CS alone are sufficient to cause inflammation or pathology in recipient mice. We found no evidence of impaired suppression of T cell proliferation among regulatory T cells from CS-exposed mice. These results suggest that CS exposure initiates an Ag-specific response that leads to pulmonary destruction and inflammation that involves both CD8(+) and CD4(+) T cells. These results are direct evidence for an autoimmune response initiated by CS exposure.