In our mouse model, we found that T lymphocytes were associated with increased apoptosis of parenchymal cells, which has been associated with emphysema in cross-sectional studies of COPD patients19,34 and other animal models.35,36 Activated CD8+ T lymphocytes can directly induce apoptosis through expression of perforin, granzymes, and Fas-ligand,37 while CD4+ T cells can contribute to apoptosis through the production of pro-apoptotic cytokines such as IFN-γ.38 However, it is also possible that apoptosis is indirect and mediated by other cell types in a T-cell dependent manner. This evidence concerns the gene PRF1 and pulmonary emphysema.