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- Title
Activation of CD8<sup>+</sup> T Cells in Chronic Obstructive Pulmonary Disease Lung.
- Authors
Villaseñor-Altamirano, Ana B.; Jain, Dhawal; Yunju Jeong; Menon, Jaivardhan A.; Kamiya, Mari; Haider, Hibah; Manandhar, Reshmi; Sheikh, Muhammad Dawood Amir; Athar, Humra; Merriam, Louis T.; Min Hyung Ryu; Takanori Sasaki; Castaldi, Peter J.; Rao, Deepak A.; Sholl, Lynette M.; Vivero, Marina; Hersh, Craig P.; Xiaobo Zhou; Veerkamp, Justus; Yun, Jeong H.
- Abstract
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. 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 Hhip1/2 murine model of COPD. Measurements and Main Results: Mild-moderate COPD lungs have increased abundance of two CD8+T cell subpopulations: cytotoxic KLRG++TIGIT+CX3CR+1 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 mildmoderate 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.
- Subjects
OBSTRUCTIVE lung diseases; CHRONIC obstructive pulmonary disease; T cells
- Publication
American Journal of Respiratory & Critical Care Medicine, 2023, Vol 208, Issue 11, p1177
- ISSN
1073-449X
- Publication type
Article
- DOI
10.1164/rccm.202305-0924OC