title: Mixed allogeneic chimerism prevents obstructive airway disease in a rat heterotopic tracheal transplant model.
abstract: BACKGROUND
  Mixed bone marrow chimerism reliably produces donor-specific transplantation tolerance for a variety of solid organ and cellular grafts. We used a rat heterotopic tracheal transplant model for chronic rejection to investigate whether mixed chimerism could successfully prevent obstructive airway disease.
  
  
  METHODS
  Mixed allogeneic chimeras were prepared by reconstituting lethally irradiated Wistar-Furth (WF) recipients with a mixture of 5 x 10(6) T-cell-depleted syngeneic (WF) and 100 x 10(6) T-cell-depleted allogeneic (ACI) bone marrow cells (ACI + WF --> WF). Mixed chimerism was present in all animals 28 days after bone marrow transplantation. Donor-specific, syngeneic, or major histocompatibility complex (MHC)-disparate allogeneic tracheas were implanted in recipient's omentum and removed for histologic analysis 30 to 150 days after transplantation.
  
  
  RESULTS
  At 30 days after implantation, median luminal obstruction grades (0=none, 4=complete) of syngeneic and allogeneic tracheas were 0 and 4, respectively. Donor-specific (ACI) tracheas implanted in chimeric (ACI + WF --> WF) recipients were remarkably free of obstruction (median luminal obstruction grade=0 at 150 days) and had excellent preservation of respiratory epithelium. Third-party F344 tracheas implanted in chimeric recipients developed progressive luminal obstruction (grade 2 at 30 days, grade 3 at 90 days).
  
  
  CONCLUSIONS
  Mixed allogeneic chimerism induces donor-specific tolerance and prevents development of the characteristic fibroproliferative obstructive lesion of bronchiolitis obliterans in a rat heterotopic tracheal transplant model. Excellent preservation of tracheal structure and morphology was achieved across major and minor histocompatibility barriers.
authors.affiliation: Division of Cardiothoracic Surgery, University of Pittsburgh Medical Center, PA 15261, USA.
authors.forename: J S
authors.initials: JS
authors.lastname: Gammie
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.forename: N
authors.initials: N
authors.lastname: Kawaharada
authors.forename: Y L
authors.initials: YL
authors.lastname: Colson
authors.forename: S
authors.initials: S
authors.lastname: Yousem
authors.forename: S T
authors.initials: ST
authors.lastname: Ildstad
authors.forename: S M
authors.initials: SM
authors.lastname: Pham
mesh_terms: D000402:Airway Obstruction / Q000209:etiology / Q000517:prevention & control*; D000818:Animals; D016026:Bone Marrow Transplantation; D002678:Chimera; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000150:complications; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014132:Trachea / Q000637:transplantation*; D016042:Transplantation, Heterotopic / Q000009:adverse effects