• Ana B Villaseñor-Altamirano, Dhawal Jain, Yunju Jeong, Jaivardhan A Menon, Mari Kamiya, Hibah Haider, Reshmi Manandhar, SheikhMuhammad Dawood AmirMDA0000-0002-5029-4161Division of Pulmonary and Critical Care Medicine., Humra Athar, Louis T Merriam, Min Hyung Ryu, Takanori Sasaki, Peter J Castaldi, Deepak A Rao, Lynette M Sholl, Marina Vivero, Craig P Hersh, Xiaobo Zhou, Justus Veerkamp, Jeong H Yun, Edy Y Kim, and MassGeneralBrigham - Bayer Pulmonary Drug Discovery Laboratory.
• Division of Pulmonary and Critical Care Medicine.
• Am. J. Respir. Crit. Care Med. 2023 Dec 1; 208 (11): 117711951177-1195.

AbstractRationale: 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. Objectives: 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, proteomic, and T-cell receptor repertoire analyses on lung tissue from patients with mild-moderate COPD (n = 5, Global Initiative for Chronic Obstructive Lung Disease 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+ TEMRA (T effector memory CD45RA+) 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 T-cell receptor clonotypes. In an independent cohort, the CD8+KLRG1+ TEMRA cells are increased in mild-moderate COPD lung compared with 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.

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