医学
质量细胞仪
免疫系统
细胞毒性T细胞
CD8型
T细胞
CD28
免疫学
肺
病理
生物
内科学
体外
表型
生物化学
基因
作者
Jia Li,Na Li,Tamim Abdelaal,Ning Guo,Marieke E. IJsselstein,Vincent van Unen,Ciska Lindelauf,Qinyue Jiang,Yanling Xiao,María Fernanda Pascutti,Pieter S. Hiemstra,Frits Koning,Jan Stolk,Padmini P. S. J. Khedoe
标识
DOI:10.1164/rccm.202303-0442oc
摘要
Chronic inflammation plays an important role in alveolar tissue damage in emphysema, but the underlying immune alterations and cellular interactions are incompletely understood.To explore disease-specific pulmonary immune cell alterations and cellular interactions in emphysema.We used single-cell mass cytometry to compare the immune compartment in alveolar tissue from 15 patients with severe emphysema and 5 controls. Imaging mass cytometry (IMC) was applied to identify altered cell-cell interactions in alveolar tissue from emphysema patients (n=12) compared to controls (n=8).We observed higher percentages of central memory CD4 T cells in combination with lower proportions of effector memory CD4 T cells in emphysema. In addition, proportions of cytotoxic central memory CD8 T cells and CD127+CD27+CD69- T cells were higher in emphysema, the latter potentially reflecting an influx of circulating lymphocytes into the lungs. Central memory CD8 T cells, isolated from alveolar tissue from emphysema patients exhibited an IFN-γ-response upon anti-CD3/anti-CD28 activation. Proportions of CD1c+ dendritic cells (DC), expressing migratory and costimulatory markers, were higher in emphysema. Importantly, IMC enabled us to visualize increased spatial colocalization of CD1c+ DC and CD8 T cells in emphysema in situ.Using single-cell CyTOF, we characterized the alterations of the immune cell signature in alveolar tissue from patients with COPD stage III/IV emphysema versus control lung tissue. These data contribute to a better understanding of the pathogenesis of emphysema and highlight the feasibility of interrogating the immune cell signature using single-cell and IMC in human lung tissue.
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