title: Regulatory T cells and liver pathology in a murine graft versus host response model.
abstract: OBJECTIVE
  We have previously reported in mice the hepatic inflammatory in graft versus host response (GVHR) model due to the disparity of major histocompatibility complex class-II. The regulatory T (Treg) cells have been reported to control excessive immune response and prevent immune-related diseases. This study aimed to investigate the pathogenesis profiles of chronic GVHR progression, focusing on the Treg cells.
  
  
  METHODS
  GVHR mice induced by parental spleen CD4(+) T cell injection were sacrificed after 0, 2, 4, and 8 weeks (G0, G2, G4, G8). Further, one GVHR group received anti-IL-10 antibody in advance and were maintained for 2 weeks. Pathologic profiles of hepatic infiltrating inflammatory cells were evaluated by haematoxylin and eosin and immunohistochemistry staining with surface markers including Treg cell markers.
  
  
  RESULTS
  Remarkable hepatic inflammatory in G2 significantly and gradually improved over time up to G8. In immunohistochemical staining, the increased IL-10 receptor beta(+) Tr1 cells in G2 were maintained through to G8; although other inflammatory cells decreased from G2 to G8. By contrast, in the anti-IL-10 antibody received-GVHR mice, the Tr1 cells were not detectable with significant inflammatory aggravation, while FoxP3(+) Treg cells significantly enhanced.
  
  
  CONCLUSIONS
  These findings in the GVHR mice suggest that the expression and activity of Treg cells, especially the Tr1 cells, might be key factors for pathologic alteration in immune-related liver disease.
authors.affiliation: Department of Development for Community Medicine, Tokyo Medical University.
authors.forename: Teruo
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Mikio
authors.initials: M
authors.lastname: Doy
authors.forename: Rie
authors.initials: R
authors.lastname: Unno
authors.forename: Akira
authors.initials: A
authors.lastname: Honda
authors.forename: Tadashi
authors.initials: T
authors.lastname: Ikegami
authors.forename: Shinichi
authors.initials: S
authors.lastname: Itoh
authors.forename: Bernard
authors.initials: B
authors.lastname: Bouscarel
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Matsuzaki