title: FK 506 inhibits tolerance induction in mice liver transplantation.
abstract: BACKGROUND
  In the orthotopic mouse liver transplantation model, allografts are accepted without immunosuppression, and donor-specific tolerance is induced upto 40 days. Although FK 506 is a well-known immunosuppressive agent, its influence on tolerance induction is not known. In this study, we examined the influence of FK 506 on tolerance induction in a mouse liver transplant model.
  
  
  METHODS
  Orthotopic liver transplantation was performed from B10.BR (H-2K) to B10.D2 (H-2D mice). In the experimental group, FK 506 (1 mg/kg/d) was given subcutaneously to the recipients from day 0 to day 21, whereas the control group received a placebo (1 mg/kg/d). On day 40, donor skin grafts were transplanted to the recipients to examine the survival times of the recipients and the skin grafts. On day 14, donor-type cells in recipient's blood, spleen, kidney, thymus, and lymph nodes were examined by RT-PCR using specific donor-type MHC class I and II primers.
  
  
  RESULTS
  All recipients survived for more than 100 days. The mean survival time of skin grafts in the experimental group was significantly reduced compared to that of controls. On day 14, either donor-type MHC class I- or class II-positive cells were detected in the control group, whereas donor-derived MHC class II-positive cells disappeared in the experimental group.
  
  
  CONCLUSIONS
  In the early period after mouse liver transplantation, FK 506 inhibits tolerance induction paradoxically. Some donor-derived MHC class II-positive cells might play an important role in tolerance induction.
authors.affiliation: Fujita University School of Medicine, Aichi, Japan. sugioka@fujita-hu.ac.jp
authors.forename: A
authors.initials: A
authors.lastname: Sugioka
authors.forename: M
authors.initials: M
authors.lastname: Morita
authors.forename: T
authors.initials: T
authors.lastname: Kato
authors.forename: S
authors.initials: S
authors.lastname: Hoshimoto
authors.forename: J
authors.initials: J
authors.lastname: Fujita
authors.forename: Z
authors.initials: Z
authors.lastname: Morise
authors.forename: A
authors.initials: A
authors.lastname: Hasumi
mesh_terms: D000818:Animals; D006085:Graft Survival / Q000187:drug effects / Q000276:immunology*; D016031:Liver Transplantation / Q000276:immunology*; D051379:Mice; D008815:Mice, Inbred Strains; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000627:therapeutic use*; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000276:immunology; D014184:Transplantation, Homologous / Q000276:immunology
chemical_list: D016559:Tacrolimus