title: Heart allograft tolerance without development of posttransplant cardiac allograft vasculopathy in chimerism-based, drug-induced tolerance.
abstract: BACKGROUND
  Recently, we have described a drug (cyclophosphamide [CP] plus busulfan [BU])-induced skin allograft tolerance in mice that can regularly overcome fully H-2-mismatched barriers. Using this method, we have investigated whether or not this regimen can prolong the survival of heart allografts and inhibit the development of posttransplant cardiac allograft vasculopathy (CAV).
  
  
  METHODS
  The components of the method are intravenous administration of 1 x 108 allogeneic spleen cells on day 0, intraperitoneal injection of 200 mg/kg of CP and 30 mg/kg of BU on day 2, and intravenous injection of T cell-depleted 1 x 107 allogeneic bone marrow cells from the same strain of mice on day 3. Heart grafting was performed on day 28. Chimerism in peripheral blood was followed by flow cytometric analysis, and histological analysis was performed at various times after grafting.
  
  
  RESULTS
  In a fully major histocompatability complex (MHC)-mismatched combination of B10.D2 (H-2d, IE+)-->B10 (H-2b, IE-), stable, multilineage-mixed chimerism was observed permanently. B10.D2 heart grafts were accepted permanently in a donor-specific manner, and posttransplant CAV did not develop.
  
  
  CONCLUSIONS
  These results demonstrated that the drug-induced tolerance recently established by us can regularly induce a long-lasting heart allograft tolerance without development of CAV.
authors.affiliation: Department of Cardiovascular Surgery, Faculty of Medicine, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Qi-Wei
authors.initials: QW
authors.lastname: Zhang
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Tomita
authors.forename: Goro
authors.initials: G
authors.lastname: Matsuzaki
authors.forename: Ichiro
authors.initials: I
authors.lastname: Shimizu
authors.forename: Toshiro
authors.initials: T
authors.lastname: Iwai
authors.forename: Shinji
authors.initials: S
authors.lastname: Okano
authors.forename: Ryosuke
authors.initials: R
authors.lastname: Minagawa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Nakashima
authors.forename: Katsuo
authors.initials: K
authors.lastname: Sueishi
authors.forename: Kikuo
authors.initials: K
authors.lastname: Nomoto
authors.forename: Hisataka
authors.initials: H
authors.lastname: Yasui
mesh_terms: D000818:Animals; D002066:Busulfan / Q000627:therapeutic use; D003520:Cyclophosphamide / Q000627:therapeutic use; D016027:Heart Transplantation / Q000276:immunology* / Q000473:pathology*; D006650:Histocompatibility Testing; D007108:Immune Tolerance; D016130:Immunophenotyping; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D017710:Lymphocyte Transfusion; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D002066:Busulfan