title: Dynamics of human regulatory T cells in lung lavages of lung transplant recipients.
abstract: BACKGROUND
  Despite advances in the field of lung transplantation, the median survival after lung transplant remains below 5 years. Early rejection is a risk factor for the development of chronic rejection. In animal models of transplant tolerance, regulatory T cells (Tregs) can prevent the establishment of rejection.
  
  
  METHODS
  This study was designed to explore the dynamics of Tregs focally and systemically in lung transplant recipients. Sequential surveillance bronchoscopy results were available in 51 patients with at least four sequential samples recovered from each patient at defined times posttransplant. In 36 individuals, a complete year of follow-up data for BAL was analyzed. In 33 of these individuals had a complete year of follow-up data for peripheral blood monocyte cell specimens were also analyzed. Lung lavage cells were recovered from each bronchoscopy and corresponding blood draw and subjected to polychromatic flow cytometry. The percentage of CD4 lymphocytes, which expressed the intracellular transcription factor FoxP3 was recorded at each point. At each time point, lung biopsy specimens were scored for rejection.
  
  
  RESULTS
  Lung Treg frequency was significantly more variable than blood Treg frequency. Treg frequency in the lung was increased in the aftermath of acute rejection. In contrast, lung Treg frequency declined sequentially in patients demonstrating continued quiescence. Mean BAL Treg level integrated over the first transplant year correlated inversely with the degree of acute cellular rejection. In contrast, blood Treg levels demonstrated no correlation with lung pathology.
  
  
  CONCLUSIONS
  Lung Tregs increase in the setting of acute cellular rejection, whereas declining levels of BAL Tregs correlates with immunologic quiescence.
authors.affiliation: McKelvey Center for Lung Transplantation and Pulmonary Vascular Diseases, Emory University School of Medicine, Atlanta, GA 30322, USA. david.neujahr@emoryhealthcare.org
authors.forename: David C
authors.initials: DC
authors.lastname: Neujahr
authors.forename: Adriana C
authors.initials: AC
authors.lastname: Cardona
authors.forename: Onome
authors.initials: O
authors.lastname: Ulukpo
authors.forename: Mark
authors.initials: M
authors.lastname: Rigby
authors.forename: Andres
authors.initials: A
authors.lastname: Pelaez
authors.forename: Allan
authors.initials: A
authors.lastname: Ramirez
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Gal
authors.forename: Seth D
authors.initials: SD
authors.lastname: Force
authors.forename: E Clinton
authors.initials: EC
authors.lastname: Lawrence
authors.forename: Allan D
authors.initials: AD
authors.lastname: Kirk
authors.forename: Christian P
authors.initials: CP
authors.lastname: Larsen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006084:Graft Rejection / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008137:Longitudinal Studies; D008168:Lung / Q000276:immunology / Q000473:pathology; D016040:Lung Transplantation / Q000276:immunology* / Q000473:pathology / Q000502:physiology; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D055815:Young Adult
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors
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