title: Regulatory T-cell impairment in cystic fibrosis patients with chronic pseudomonas infection.
abstract: BACKGROUND
  Patients with cystic fibrosis (CF) lung disease have chronic airway inflammation driven by disrupted balance of T-cell (Th17 and Th2) responses. Regulatory T cells (Tregs) dampen T-cell activation, but their role in CF is incompletely understood.
  
  
  OBJECTIVE
  To characterize numbers, function, and clinical impact of Tregs in CF lung disease.
  
  
  METHODS
  Tregs were quantified in peripheral blood and airway samples from patients with CF and from lung disease control patients without CF and healthy control subjects. The role of Pseudomonas aeruginosa and CF transmembrane conductance regulator (CFTR) in Treg regulation was analyzed by using in vitro and murine in vivo models.
  
  
  RESULTS
  Tregs were decreased in peripheral blood and airways of patients with CF compared with healthy controls or lung disease patients without CF and correlated positively with lung function parameters. Patients with CF with chronic P. aeruginosa infection had lower Tregs compared with patients with CF without P. aeruginosa infection. Genetic knockout, pharmacological inhibition, and P. aeruginosa infection studies showed that both P. aeruginosa and CFTR contributed to Treg dysregulation in CF. Functionally, Tregs from patients with CF or from Cftr(-/-) mice were impaired in suppressing conventional T cells, an effect that was enhanced by P. aeruginosa infection. The loss of Tregs in CF affected memory, but not naive Tregs, and manifested gradually with disease progression.
  
  
  CONCLUSIONS
  Patients with CF who have chronic P. aeruginosa infection show an age-dependent, quantitative, and qualitative impairment of Tregs. Modulation of Tregs represents a novel strategy to rebalance T-cell responses, dampen inflammation, and ultimately improve outcomes for patients with infective CF lung disease.
authors: 1 Children's Hospital and.
authors: Andreas
authors: A
authors: Hector
authors: Heike
authors: H
authors: Schäfer
authors: Simone
authors: S
authors: Pöschel
authors: Alexandra
authors: A
authors: Fischer
authors: Benedikt
authors: B
authors: Fritzsching
authors: Anjali
authors: A
authors: Ralhan
authors: Melanie
authors: M
authors: Carevic
authors: Hasan
authors: H
authors: Öz
authors: Sabine
authors: S
authors: Zundel
authors: Michael
authors: M
authors: Hogardt
authors: Martina
authors: M
authors: Bakele
authors: Nikolaus
authors: N
authors: Rieber
authors: Joachim
authors: J
authors: Riethmueller
authors: Ute
authors: U
authors: Graepler-Mainka
authors: Mirjam
authors: M
authors: Stahl
authors: Annika
authors: A
authors: Bender
authors: Julia-Stefanie
authors: JS
authors: Frick
authors: Marcus
authors: M
authors: Mall
authors: Dominik
authors: D
authors: Hartl
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D002648:Child; D002675:Child, Preschool; D003550:Cystic Fibrosis / Q000150:complications* / Q000276:immunology*; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D011552:Pseudomonas Infections / Q000150:complications*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D055815:Young Adult
keywords: Tregs; cystic fibrosis; immunity; lung; regulatory T cells