title: Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis.
abstract: BACKGROUND
  The implication of T cells in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is controversial. CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are pivotal in maintaining immune homeostasis, but their role in IPF pathophysiology has not yet been studied.
  
  
  OBJECTIVE
  To explore Treg dynamics and function in IPF.
  
  
  METHODS
  Treg levels and dynamics were analyzed by flow cytometry in the peripheral blood (PB) and bronchoalveolar lavage (BAL) of 21 patients with IPF, 35 patients with lung diseases other than IPF (patients without IPF), 20 patients with collagen vascular diseases with pulmonary parenchymal involvement (CVD-IP), and 28 healthy volunteers. The suppression of autologous CD4(+)CD25(-) cell-proliferative responses and cytokine release by magnetic bead-isolated Tregs was evaluated by proliferation assays and cytometric bead array. Correlations of Treg function and levels with lung function parameters were also performed.
  
  
  RESULTS
  In patients with IPF, both BAL and PB Tregs were reduced compared with those of healthy volunteers and patients without IPF, although not always significantly. Treg levels were not affected by the administration of low-dose prednisone in four nonresponding patients. The suppressor potential of BAL and PB Tregs was compromised in patients with IPF and patients with CVD-IP, compared with healthy volunteers and patients without IPF. Similarly, the Treg-induced suppression of helper T-cell type 1 and 2 cytokine secretion was impaired in the BAL of patients with IPF and patients with CVD-IP. Moreover, the defective function of BAL Tregs correlated highly with parameters of disease severity.
  
  
  CONCLUSIONS
  This study provides the first evidence of global Treg impairment in IPF that strongly correlates with disease severity, suggesting a role for Tregs in the fibrotic process.
authors.affiliation: Department of Hematology, Democritus University of Thrace, Medical School Dragana, Alexandroupolis, Greece. ikotsian@med.duth.gr
authors.forename: Ioannis
authors.initials: I
authors.lastname: Kotsianidis
authors.forename: Evangelia
authors.initials: E
authors.lastname: Nakou
authors.forename: Irene
authors.initials: I
authors.lastname: Bouchliou
authors.forename: Argyrios
authors.initials: A
authors.lastname: Tzouvelekis
authors.forename: Emmanouil
authors.initials: E
authors.lastname: Spanoudakis
authors.forename: Paschalis
authors.initials: P
authors.lastname: Steiropoulos
authors.forename: Ioannis
authors.initials: I
authors.lastname: Sotiriou
authors.forename: Vassilis
authors.initials: V
authors.lastname: Aidinis
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Margaritis
authors.forename: Costas
authors.initials: C
authors.lastname: Tsatalas
authors.forename: Demosthenes
authors.initials: D
authors.lastname: Bouros