title: Long-term tolerance to kidney allografts after induced rejection of donor hematopoietic chimerism in a preclinical canine model.
abstract: BACKGROUND
  Allogeneic hematopoietic cell transplantation provides a reliable method for inducing tolerance toward solid organ grafts. However, this procedure can result in graft-versus-host disease, thereby limiting its application. Here, we test the hypothesis that mixed chimerism can be intentionally reverted to host hematopoiesis without rejection of a kidney graft.
  
  
  METHODS
  Recipient dogs were given 2-Gy total-body irradiation (TBI) before and a short course of immunosuppression after marrow infusion from dog leukocyte antigen-identical littermates. All dogs achieved stable mixed chimerism. After a mean of 20 weeks, one cohort of dogs received kidney transplants from their respective marrow donors. Subsequently, recipients were reconditioned with 2-Gy TBI and given autologous granulocyte colony-stimulating factor-mobilized leukocytes (recipient leukocyte infusion [RLI]) that had been collected before marrow transplantation.
  
  
  RESULTS
  Dogs receiving a second TBI and RLI without a kidney transplant rejected their donor hematopoietic graft within 3 weeks. Dogs that received kidney grafts, followed by a second TBI and RLI, rejected their marrow graft without rejecting their transplanted kidneys for periods greater than 1 year.
  
  
  CONCLUSIONS
  Mixed chimerism may be clinically reverted to 100% recipient without rejection of a kidney allograft. This finding may have application toward minimizing the risk of graft-versus-host disease in solid organ transplantation patients given hematopoietic cell transplantation from human leukocyte antigen-identical donors.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA. sgraves@fhcrc.org
authors.forename: Scott S
authors.initials: SS
authors.lastname: Graves
authors.forename: David W
authors.initials: DW
authors.lastname: Mathes
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: Christian S
authors.initials: CS
authors.lastname: Kuhr
authors.forename: Jeff
authors.initials: J
authors.lastname: Chang
authors.forename: Tiffany M
authors.initials: TM
authors.lastname: Butts
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
mesh_terms: D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology*; D004285:Dogs; D006084:Graft Rejection / Q000276:immunology*; D006085:Graft Survival; D006086:Graft vs Host Disease / Q000276:immunology; D006410:Hematopoiesis / Q000276:immunology*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D016030:Kidney Transplantation / Q000276:immunology*; D017708:Leukocyte Transfusion; D023421:Models, Animal; D013997:Time Factors; D018183:Transplantation Chimera; D019172:Transplantation Conditioning; D023001:Transplantation Tolerance; D014916:Whole-Body Irradiation
chemical_list: D015395:Histocompatibility Antigens Class I; C039692:histocompatibility antigen DLA