Activation of CD8 T Cells in Chronic Obstructive Pulmonary Disease Lung.

Despite the importance of inflammation in chronic obstructive pulmonary disease (COPD), the immune cell landscape in the lung tissue of patients with mild-moderate disease has not been well characterized at the single-cell and molecular level. To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution. We performed single-cell transcriptomic, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD ( = 5, Global Initiative for Chronic Obstructive Lung Disease I or II), emphysema without airflow obstruction ( = 5), end-stage COPD ( = 2), control ( = 6), or donors ( = 4). We validated in an independent patient cohort ( = 929) and integrated with the murine model of COPD. Mild-moderate COPD lungs have increased abundance of two CD8 T cell subpopulations: cytotoxic KLRG1TIGITCX3CR1 TEMRA (T effector memory CD45RA) cells, and DNAM-1CCR5 T resident memory (T) cells. These CD8 T cells interact with myeloid and alveolar type II cells via and have hyperexpanded T-cell receptor clonotypes. In an independent cohort, the CD8KLRG1 TEMRA cells are increased in mild-moderate COPD lung compared with control or end-stage COPD lung. Human CD8KLRG1 TEMRA cells are similar to CD8 T cells driving inflammation in an aging-related murine model of COPD. CD8 TEMRA cells are increased in mild-moderate COPD lung and may contribute to inflammation that precedes severe disease. Further study of these CD8 T cells may have therapeutic implications for preventing severe COPD.