title: Development and maintenance of donor-specific chimerism in semi-allogenic and fully major histocompatibility complex mismatched facial allograft transplants.
abstract: BACKGROUND
  The clinical application of composite tissue allograft transplants opened the discussion on the restoration of facial deformities by allotransplantation. We introduce a hemifacial allograft transplant model to investigate the rationale for the development of operational tolerance across a major histocompatibility complex (MHC) barrier.
  
  
  METHODS
  Thirty rats were studied in five groups of six animals each. The composite hemiface isograft transplantations were performed in group 1. Allograft rejection controls included semi-allogenic transplantations from LBN (RT1(1+n) donors (group 2) and fully allogenic transplantations from ACI (RT1a) donors (group 3) to LEW (RT1(1)) recipients. In the allograft treatment groups, recipients of LBN (group 4) and ACI donors (group 5) were treated with cyclosporine A monotherapy (16 mg/kg/day, tapered to 2 mg/kg/day). Face allografts were evaluated clinically and histologically. Donor-specific chimerism for MHC class I RT1n and RT1a antigens was assessed by flow cytometry. Mixed lymphocyte reaction for donor-specific tolerance in vitro was tested at day 160 posttransplant.
  
  
  RESULTS
  Isograft controls survived indefinitely. All nontreated allografts rejected within 5 to 8 days posttransplant. Long-term survival was achieved in 100% of LBN (up to 400 days) and ACI (up to 330 days) recipients. At day 160, posttransplant donor-specific chimerism was present in recipients of LBN (10.14% CD4/RT1n, 6.38% CD8/RT1n, 10.02% CD45RA/RT1n) and ACI (17.54% CD4/RT1a, 9.28% CD8/RT1a) transplants, and mixed lymphocyte reaction confirmed tolerance in recipients of LBN transplants and moderate reactivity in recipients of ACI allografts.
  
  
  CONCLUSIONS
  Operational tolerance was induced in hemiface allograft transplants across an MHC barrier under cyclosporine A monotherapy protocol. It was associated directly with the presence of multilineage donor-specific chimerism.
authors.affiliation: Department of Plastic Surgery, Microsurgery Laboratory, L14, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. siemiom@ccf.org
authors.forename: Maria
authors.initials: M
authors.lastname: Siemionow
authors.forename: Yavuz
authors.initials: Y
authors.lastname: Demir
authors.forename: Abir
authors.initials: A
authors.lastname: Mukherjee
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Klimczak
mesh_terms: D000818:Animals; D046528:Chimerism; D016572:Cyclosporine / Q000627:therapeutic use; D005145:Face / Q000601:surgery*; D005434:Flow Cytometry; D006650:Histocompatibility Testing; D007108:Immune Tolerance; D007150:Immunohistochemistry; D007959:Lymphocyte Culture Test, Mixed; D051381:Rats; D011912:Rats, Inbred ACI; D011914:Rats, Inbred BN; D011917:Rats, Inbred Lew; D016038:Skin Transplantation; D014019:Tissue Donors; D018183:Transplantation Chimera; D014184:Transplantation, Homologous
chemical_list: D016572:Cyclosporine