Publication

Pulmonary exacerbations in early cystic fibrosis lung disease are marked by strong modulation of CD3 and PD-1 on luminal T cells

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Last modified
  • 06/25/2025
Type of Material
Authors
    Vincent D. Giacalone, Emory UniversityDiego Mauricio Moncada Giraldo, Emory UniversityGeorge L. Silva, Emory UniversityJustin Hosten, Emory UniversityLimin Peng, Emory UniversityLokesh Guglani, Emory UniversityRabindra M. Tirouvanziam, Emory University
Language
  • English
Date
  • 2023-09-21
Publisher
  • Frontiers
Publication Version
Copyright Statement
  • © 2023 Giacalone, Giraldo, Silva, Hosten, Peng, Guglani and Tirouvanziam
License
Final Published Version (URL)
Title of Journal or Parent Work
Volume
  • 14
Start Page
  • 1194253
Grant/Funding Information
  • This study was supported by a grant from the Cystic Fibrosis Foundation (TIROUV19A0) and the Hertz Family Foundation.
Supplemental Material (URL)
Abstract
  • Background In chronic cystic fibrosis (CF) lung disease, neutrophilic inflammation and T-cell inhibition occur concomitantly, partly due to neutrophil-mediated release of the T-cell inhibitory enzyme Arg1. However, the onset of this tonic inhibition of T cells, and the impact of pulmonary exacerbations (PEs) on this process, remain unknown. Methods Children with CF aged 0-5 years were enrolled in a longitudinal, single-center cohort study. Blood (n = 35) and bronchoalveolar lavage (BAL) fluid (n = 18) were collected at stable outpatient clinic visits or inpatient PE hospitalizations and analyzed by flow cytometry (for immune cell presence and phenotype) and 20-plex chemiluminescence assay (for immune mediators). Patients were categorized by PE history into (i) no prior PE, (ii) past history of PE prior to stable visit, or (iii) current PE. Results PEs were associated with increased concentration of both pro- and anti-inflammatory mediators in BAL, and increased neutrophil frequency and G-CSF in circulation. PE BAL samples showed a trend toward an increased frequency of hyperexocytic “GRIM” neutrophils, which we previously identified in chronic CF. Interestingly, expression levels of the T-cell receptor associated molecule CD3 and of the inhibitory programmed death-1 (PD-1) receptor were respectively decreased and increased on T cells from BAL compared to blood in all patients. When categorized by PE status, CD3 and PD-1 expression on blood T cells did not differ among patients, while CD3 expression was decreased, and PD-1 expression was increased on BAL T cells from patients with current PE. Conclusions Our findings suggest that airway T cells are engaged during early-life PEs, prior to the onset of chronic neutrophilic inflammation in CF. In addition, increased blood neutrophil frequency and a trend toward increased BAL frequency of hyperexocytic neutrophils suggest that childhood PEs may progressively shift the balance of CF airway immunity towards neutrophil dominance.
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Keywords
Research Categories
  • Biology, Cell
  • Health Sciences, Immunology

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