title: Time elapsed after transplantation influences the relationship between the number of regulatory T cells in lung allograft biopsies and subsequent acute rejection episodes.
abstract: BACKGROUND
  Regulatory T lymphocytes (Tregs) play an important role in acute rejection after lung transplantation. However, the importance of the time elapsed after transplantation on the Treg response requires further investigation. We aim to evaluate the change over time in the frequency of Tregs in lung allograft biopsies and to assess how Tregs relate to simultaneous and subsequent acute cellular rejection.
  
  
  METHODS
  A total of 258 biopsy samples obtained 0.5, 1, 3, 12 and 24 months after transplantation from 58 consecutive lung transplant patients were included. The biopsies were scored for acute rejection according to the ISHLT criteria (A0-A4) and immunohistochemically stained with antibodies against FoxP3.
  
  
  RESULTS
  There was a tendency for a decrease in the number of Tregs/mm2 with time. However, the previous levels of Tregs/mm2 did not have any significant effect on future levels of Tregs/mm2. For biopsies taken 0.5 and 1 month after transplantation, a significant correlation between Tregs/mm2 and the degree of acute rejection was found, and logistic regression analysis using updated values for Tregs/mm2 showed a significant relationship between Tregs/mm2 at 2 weeks and an A-score≥2 after 1 and 3 months. At later time points, this correlation disappeared.
  
  
  CONCLUSIONS
  Our data indicate that the time elapsed after transplantation is an important parameter influencing the Treg response after lung transplantation. This observation is in accordance with studies indicating a narrow therapeutic window for induction of tolerance by specifically targeting T-cells. The results also indirectly indicate that Tregs early after transplantation could have an impact on the long-term outcome.
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark. Electronic address: dorrit.krustrup@regionh.dk.
authors.forename: Dorrit
authors.initials: D
authors.lastname: Krustrup
authors.affiliation: The Heart and Lung Transplantation Unit, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Martin
authors.initials: M
authors.lastname: Iversen
authors.affiliation: Department of Biostatistics, University of Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Martinussen
authors.affiliation: Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Denmark.
authors.forename: Claus B
authors.initials: CB
authors.lastname: Andersen
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D064591:Allografts; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000276:immunology* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D016040:Lung Transplantation; D008297:Male; D008875:Middle Aged; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D013997:Time Factors; D055815:Young Adult
keywords: Acute rejection; FoxP3; Lung transplantation; Regulatory T cell