Correlation of donor leukocyte chimerism with pulmonary allograft survival after immunosuppressive drug withdrawal in a porcine model.
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.
Kruse
Bianca
B
Division of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany.
Thissen
Stefanie
S
Warnecke
Gregor
G
Avsar
Murat
M
Gottlieb
Jens
J
Hohlfeld
Jens M
JM
Karstens
Johann H
JH
Kaever
Volkhard
V
Länger
Florian
F
Pabst
Brigitte
B
Ungefroren
Hendrik
H
Haverich
Axel
A
Strüber
Martin
M
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
D007166:Immunosuppressive Agents