Mixed allogeneic chimerism prevents obstructive airway disease in a rat heterotopic tracheal transplant model.
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.
Gammie
J S
JS
Division of Cardiothoracic Surgery, University of Pittsburgh Medical Center, PA 15261, USA.
Li
S
S
Kawaharada
N
N
Colson
Y L
YL
Yousem
S
S
Ildstad
S T
ST
Pham
S M
SM
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