Operational tolerance to class I disparate lungs can be induced despite pretransplant immunization with class I allopeptides.
BACKGROUND
Using a class I-disparate swine lung transplant model, we examined whether an intensive course of tacrolimus could induce operational tolerance and whether preoperative allopeptide immunization would prevent the development of tolerance.


METHODS
Left lung grafts were performed using class I-disparate (class II-matched) donors. Recipients were treated with 12 days of postoperative tacrolimus. Three recipients were immunized prior to transplantation with class I allopeptides. Three other recipients were not immunized.


RESULTS
The nonimmunized recipients maintained their grafts long term (>497, >451, and >432 days), without developing chronic rejection. The immunized swine also maintained their grafts long term (>417, >402, >401 days), despite developing a variety of in vitro and in vivo responses to the immunizing peptides, as well as having strong mixed lymphocyte reactions to donor cells prior to transplantation.


CONCLUSIONS
Using only a brief course of tacrolimus, we have been able to induce a state of operational tolerance in a class I-disparate preclinical lung transplant model. Moreover, preoperative alloimmunization did not block tolerance induction or induce chronic rejection. These data show that it is possible to create a state of operational tolerance to lung allografts even in the presence of donor-sensitized cells.
Shoji
Tsuyoshi
T
Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Sahara
Hisashi
H
Muniappan
Ashok
A
Guenther
Dax A
DA
Wain
John C
JC
Houser
Stuart L
SL
Bravard
Marjory A
MA
Pujara
Akshat C
AC
Hasse
Rebecca S
RS
Sachs
David H
DH
Madsen
Joren C
JC
Allan
James S
JS
D000818:Animals; D006085:Graft Survival / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology*; D006967:Hypersensitivity / Q000276:immunology; D007108:Immune Tolerance / Q000187:drug effects / Q000276:immunology*; D016040:Lung Transplantation / Q000276:immunology*; D010455:Peptides / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D013552:Swine; D013556:Swine, Miniature; D016559:Tacrolimus / Q000494:pharmacology; D013997:Time Factors; D014184:Transplantation, Homologous / Q000276:immunology
D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016559:Tacrolimus