title: Operational tolerance to class I disparate lungs can be induced despite pretransplant immunization with class I allopeptides.
abstract: 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.
authors: Transplantation Biology Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
authors: Tsuyoshi
authors: T
authors: Shoji
authors: Hisashi
authors: H
authors: Sahara
authors: Ashok
authors: A
authors: Muniappan
authors: Dax A
authors: DA
authors: Guenther
authors: John C
authors: JC
authors: Wain
authors: Stuart L
authors: SL
authors: Houser
authors: Marjory A
authors: MA
authors: Bravard
authors: Akshat C
authors: AC
authors: Pujara
authors: Rebecca S
authors: RS
authors: Hasse
authors: David H
authors: DH
authors: Sachs
authors: Joren C
authors: JC
authors: Madsen
authors: James S
authors: JS
authors: Allan
mesh_terms: 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
chemical_list: D015395:Histocompatibility Antigens Class I; D010455:Peptides; D016559:Tacrolimus