title: Correlation of donor leukocyte chimerism with pulmonary allograft survival after immunosuppressive drug withdrawal in a porcine model.
abstract: BACKGROUND
  This study was designed to analyze the role of postoperative donor cell chimerism for the induction and maintenance of transplantation tolerance in a porcine lung transplantation model.
  
  
  METHODS
  Left-sided single lung transplantation from major histocompatibility mismatched male donors was performed in 27 female minipigs. All received a 28-day course of pharmacologic immunosuppression using various agents, some in combination with preoperative irradiation. Groups for eventual analysis were strictly defined by outcome, that is, pigs with acute rejection before postoperative day 178 (n=16) were allocated into one group, long-term surviving animals (n=11) into the other. Peripheral blood chimerism was monitored by flow cytometry and real-time polymerase chain reaction. Intragraft chimerism was detected from bronchoalveolar lavage fluid (BALF) by fluorescent in situ hybridization.
  
  
  RESULTS
  Blood chimerism peaked 1 hour after transplantation and was significantly higher in the group of long-term survivors at that time. Thereafter chimerism rapidly decreased, but tended to remain higher in long-term survivors. In case of acute rejection donor cells were lost, but remained detectable for up to 36 postoperative months in tolerant animals. In BALF, the percentage of male nuclei was equally high under immunosuppression in both groups. Rejecting animals showed a rapid decrease of Y-bearing cells in BALF after drug withdrawal and an almost complete loss when acute rejection occurred. In tolerant pigs, intragraft chimerism remained detectable throughout the follow-up.
  
  
  CONCLUSIONS
  This study demonstrates a clear correlation of donor leukocyte chimerism with long-term allograft survival in a porcine allogeneic lung transplantation model.
authors.affiliation: Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
authors.forename: Bianca
authors.initials: B
authors.lastname: Kruse
authors.forename: Stefanie
authors.initials: S
authors.lastname: Thissen
authors.forename: Gregor
authors.initials: G
authors.lastname: Warnecke
authors.forename: Murat
authors.initials: M
authors.lastname: Avsar
authors.forename: Jens
authors.initials: J
authors.lastname: Gottlieb
authors.forename: Jens M
authors.initials: JM
authors.lastname: Hohlfeld
authors.forename: Johann H
authors.initials: JH
authors.lastname: Karstens
authors.forename: Volkhard
authors.initials: V
authors.lastname: Kaever
authors.forename: Florian
authors.initials: F
authors.lastname: Länger
authors.forename: Brigitte
authors.initials: B
authors.lastname: Pabst
authors.forename: Hendrik
authors.initials: H
authors.lastname: Ungefroren
authors.forename: Axel
authors.initials: A
authors.lastname: Haverich
authors.forename: Martin
authors.initials: M
authors.lastname: Strüber
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D004334:Drug Administration Schedule; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D006085:Graft Survival / Q000276:immunology*; D006650:Histocompatibility Testing; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D017708:Leukocyte Transfusion; D016040:Lung Transplantation / Q000276:immunology*; D008285:Major Histocompatibility Complex; D008297:Male; D023421:Models, Animal; D016133:Polymerase Chain Reaction; D013375:Substance Withdrawal Syndrome / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D018183:Transplantation Chimera; D023001:Transplantation Tolerance / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents