title: Initial in vivo experience of pig artery patch transplantation in baboons using mutant MHC (CIITA-DN) pigs.
abstract: BACKGROUND
  In the pig-to-nonimmunosuppressed baboon artery patch model, a graft from an α1,3-galactosyltransferase gene-knockout pig transgenic for human CD46 (GTKO/CD46) induces a significant adaptive immune response (elicited anti-pig antibody response, increase in T cell proliferation on MLR, cellular infiltration of the graft), which is effectively prevented by anti-CD154mAb-based therapy.
  
  
  METHODS
  As anti-CD154mAb is currently not clinically applicable, we evaluated whether it could be replaced by CD28/B7 pathway blockade or by blockade of both pathways (using belatacept + anti-CD40mAb [2C10R4]). We further investigated whether a patch from a GTKO/CD46 pig with a mutant human MHC class II transactivator (CIITA-DN) gene would allow reduction in the immunosuppressive therapy administered.
  
  
  RESULTS
  When grafts from GTKO/CD46 pigs were transplanted with blockade of both pathways, a minimal or insignificant adaptive response was documented. When a GTKO/CD46/CIITA-DN graft was transplanted, but no immunosuppressive therapy was administered, a marked adaptive response was documented. In the presence of CD28/B7 pathway blockade (abatacept or belatacept), there was a weak adaptive response that was diminished when compared with that to a GTKO/CD46 graft. Blockade of both pathways prevented an adaptive response.
  
  
  CONCLUSIONS
  Although expression of the mutant MHC CIITA-DN gene was associated with a reduced adaptive immune response when immunosuppressive therapy was inadequate, when blockade of both the CD40/CD154 and CD28/B7 pathways was present, the response even to a GTKO/CD46 graft was suppressed. This was confirmed after GTKO/CD46 heart transplantation in baboons.
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: H
authors: H
authors: Iwase
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA; Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy.
authors: B
authors: B
authors: Ekser
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: V
authors: V
authors: Satyananda
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA; Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors: H
authors: H
authors: Zhou
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: H
authors: H
authors: Hara
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: P
authors: P
authors: Bajona
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: M
authors: M
authors: Wijkstrom
authors: Department of Cardiac Surgery, University of Pittsburgh, Pittsburgh, PA, USA.
authors: J K
authors: JK
authors: Bhama
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: C
authors: C
authors: Long
authors: Department of Surgery, Transplantation and Advanced Technologies, Vascular Surgery and Organ Transplant Unit, University Hospital of Catania, Catania, Italy.
authors: M
authors: M
authors: Veroux
authors: Center for Kidney Transplantation, Second Affiliated Hospital of the University of South China, Hengyang, Hunan, China.
authors: Y
authors: Y
authors: Wang
authors: Revivicor, Blacksburg, VA, USA.
authors: Y
authors: Y
authors: Dai
authors: Revivicor, Blacksburg, VA, USA.
authors: C
authors: C
authors: Phelps
authors: Revivicor, Blacksburg, VA, USA.
authors: D
authors: D
authors: Ayares
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA.
authors: M B
authors: MB
authors: Ezzelarab
authors: Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: cooperdk@upmc.edu.
authors: D K C
authors: DK
authors: Cooper
mesh_terms: D000818:Animals; D030801:Animals, Genetically Modified; D001158:Arteries / Q000637:transplantation*; D006085:Graft Survival / Q000235:genetics / Q000276:immunology; D064593:Heterografts; D006801:Humans; D009687:Nuclear Proteins / Q000235:genetics / Q000276:immunology; D016377:Organ Transplantation; D010215:Papio; D013552:Swine; D015534:Trans-Activators / Q000235:genetics / Q000276:immunology; D023001:Transplantation Tolerance / Q000235:genetics*
chemical_list: C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators
keywords: Anti-CD40 monoclonal antibody; Artery patch; CTLA4-Ig; Costimulation blockade; Pig; Xenotransplantation