title: Decreased CTLA4(+) and Foxp3(+) CD25(high)CD4(+) cells in induced sputum from patients with mild atopic asthma.
abstract: BACKGROUND
  Details of the comparisons between airway and peripheral blood regulatory T cells (Tregs) in patients with atopic asthma are still unclear. The objective of this study is to investigate the profiles of both airway and circulating Tregs in atopic asthma.
  
  
  METHODS
  We measured the numbers of Tregs and eosinophils in induced sputum and peripheral blood in 28 patients with mild atopic asthma and compared these with numbers in 18 healthy controls. The frequency (%) of Tregs (surface CTLA4+, intracellular Foxp3+, and CTLA4+Foxp3+ on CD25highCD4+ T cells) in sputum and blood was determined by intracellular 5-color flow cytometry. We also correlated the numbers with the level of airway hyperresponsiveness (AHR) in asthmatics.
  
  
  RESULTS
  The mean frequencies of cells expressing CTLA4+ (19.4 ± 2.1%, p = 0.075), Foxp3+ (16.4 ± 3.3%, p = 0.001), and CTLA4+Foxp3+ (7.0 ± 1.1%, p = 0.008) in induced sputum from asthmatics were significantly lower than controls (27.2 ± 3.7%, 37.4 ± 4.7%, and 18.2 ± 3.6%, respectively), whereas in peripheral blood, there was no inter-group difference in the frequencies of cells expressing CTLA4+ (7.1 ± 1.5% vs 5.7 ± 1.7%, p > 0.05), Foxp3+ (35.7 ± 3.2% vs 21.1 ± 3.9%, p > 0.05), and CTLA4+Foxp3+ (6.6 ± 1.5% vs 4.2 ± 1.0%, p > 0.05). Moreover, the frequency of CD25highCD4+ cells expressing CTLA4+, but not Foxp3+, in induced sputum was associated with AHR (r = 0.60, p = 0.009) and airway eosinophilic inflammation (r = -0.60, p = 0.008) in asthmatics.
  
  
  CONCLUSIONS
  Airway, but not circulating, Tregs are decreased in mild atopic asthmatics, and are negatively correlated to an increase of airway eosinophilic inflammation and AHR.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Fukuoka, Japan. kawayama_tomotaka@med.kurume−u.ac.jp
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsunaga
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Kaku
authors.forename: Kyoko
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Paul M
authors.initials: PM
authors.lastname: O'Byrne
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000328:Adult; D001249:Asthma / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D060908:CTLA-4 Antigen / Q000378:metabolism*; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006969:Hypersensitivity, Immediate / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D013183:Sputum / Q000166:cytology / Q000276:immunology*; D055815:Young Adult
chemical_list: D060908:CTLA-4 Antigen; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit