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

Autor:	Giacalone VD; Department of Pediatrics, Emory University, Atlanta, GA, United States.; Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, United States., Giraldo DM; Department of Pediatrics, Emory University, Atlanta, GA, United States.; Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, United States., Silva GL; Department of Pediatrics, Emory University, Atlanta, GA, United States.; Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, United States., Hosten J; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States., Peng L; Department of Biostatistics and Bioinformatics, Emory University School of Public Health, Atlanta, GA, United States., Guglani L; Department of Pediatrics, Emory University, Atlanta, GA, United States.; Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, United States., Tirouvanziam R; Department of Pediatrics, Emory University, Atlanta, GA, United States.; Center for CF and Airways Disease Research, Children's Healthcare of Atlanta, Atlanta, GA, United States.; Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2023 Sep 21; Vol. 14, pp. 1194253. Date of Electronic Publication: 2023 Sep 21 (Print Publication: 2023).
DOI:	10.3389/fimmu.2023.1194253
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2023 Giacalone, Giraldo, Silva, Hosten, Peng, Guglani and Tirouvanziam.)
Databáze:	MEDLINE
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