title: The number of regulatory T cells in transbronchial lung allograft biopsies is related to FoxP3 mRNA levels in bronchoalveolar lavage fluid and to the degree of acute cellular rejection.
abstract: BACKGROUND
  The transcription factor Forkhead Box P3 (FoxP3) is a marker of regulatory T cells (Tregs) - a subset of T cells known to suppress a wide range of immune responses. These cells are considered to be pivotal for the induction of tolerance to donor antigens in human allografts. We aimed to correlate the number of lymphocytes expressing FoxP3 in transbronchial biopsies from lung allografts with the FoxP3 expression in bronchoalveolar lavage fluid (BALF). In addition, we aimed to correlate the number of FoxP3+ cells in transbronchial biopsies with the degree of acute cellular rejection in lung allografts.
  
  
  METHODS
  The expression of FoxP3 was evaluated using immunohistochemical staining in 40 lung allograft biopsies obtained from 23 patients. The number of Tregs was related to the FoxP3 mRNA levels as determined using qRT-PCR in corresponding BALF samples from the same patients. Furthermore, the number of Tregs was related to the degree of acute allograft rejection (according to ISHLT criteria, A0-A4).
  
  
  RESULTS
  Regression analysis showed a significant concordance between the number of Tregs in lung tissue and the level of FoxP3 mRNA relative to glyceraldehyde 3-phosphate dehydrogenase (GAPDH) mRNA levels in BALF (n=40, p=0.0001). In addition, we found a significant increase in the number of Tregs during acute allograft rejections of grades A2 and higher (median: 32.6Tregs/mm(2)) when compared to those of grades A1 and A0 (median: 4.9Tregs/mm(2)) (p=0.0002).
  
  
  CONCLUSIONS
  The association between the distribution of Tregs in transbronchial biopsies and the level of FoxP3 mRNA in BALF indicates that assessment of FoxP3 mRNA in BALF is a reliable non-invasive method for evaluating the number of Tregs in lung tissue. Furthermore, the association between the number of Tregs in lung tissue and the degree of acute cellular rejection shows that Tregs are recruited to the site of inflammation and may be involved in the regulation of acute rejection. Thus, Tregs may play a role in the cellular processes that affect lung allograft outcome.
authors: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Blegdamsvej 9, 2100 Copenhagen, Denmark. Electronic address: dorrit.krustrup@regionh.dk.
authors: Dorrit
authors: D
authors: Krustrup
authors: Caroline B
authors: CB
authors: Madsen
authors: Martin
authors: M
authors: Iversen
authors: Lars
authors: L
authors: Engelholm
authors: Lars P
authors: LP
authors: Ryder
authors: Claus B
authors: CB
authors: Andersen
mesh_terms: D000328:Adult; D064591:Allografts; D018893:Bronchoalveolar Lavage; D005260:Female; D051858:Forkhead Transcription Factors / Q000096:biosynthesis / Q000276:immunology*; D006084:Graft Rejection / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007111:Immunity, Cellular; D008168:Lung / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000096:biosynthesis / Q000276:immunology*; D012189:Retrospective Studies; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
chemical_list: C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D012333:RNA, Messenger
keywords: Allograft rejection; FoxP3; Lung transplantation; Regulatory T cell