Activation of CD8+ T Cells in COPD Lung

scRNA-seq dataset from the paper https://doi.org/10.1164/rccm.202305-0924OC 

Rationale: 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.

Objective: To define the immune cell landscape in lung tissue from patients with mild-moderate COPD at single-cell resolution.

Methods: We performed single-cell transcriptomic (RNA-seq), proteomic (CITE-seq), and T cell receptor repertoire analysis on lung tissue from patients with mild-moderate COPD (n=5, GOLD I or II), emphysema without airflow obstruction (n=5), end-stage COPD (n=2), control (n=6), or donors (n=4). We validated in an independent patient cohort (N=929) and integrated with the Hhip(+/-) murine model of COPD.

Measurements and main results: Mild-moderate COPD lungs have increased abundance of two CD8+ T cell subpopulations: cytotoxic KLRG1+TIGIT+CX3CR1+T effector memory CD45RA+(TEMRA) cells; and DNAM-1+CCR5+T resident memory (TRM) cells. These CD8+ T cells interact with myeloid and alveolar type II cells via IFNG and have hyperexpanded TCR clonotypes. In an independent cohort, the CD8+KLRG1+TEMRA gene signature is increased in mild-moderate COPD lung compared to control or end-stage COPD lung. Human CD8+KLRG1+TEMRA cells are similar to CD8+ T cells driving inflammation in an aging-related, murine model of COPD.

Conclusions: 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.