Long-term tolerance to kidney allografts after induced rejection of donor hematopoietic chimerism in a preclinical canine model

Scott S. Graves*, David W. Mathes, George E. Georges, Christian S. Kuhr, Jeff Chang, Tiffany M. Butts, Rainer Storb

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

17 Scopus citations

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. CONCLUSION: 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.

Original languageEnglish (US)
Pages (from-to)562-568
Number of pages7
JournalTransplantation
Volume94
Issue number6
DOIs
StatePublished - Sep 27 2012

Keywords

  • Dog
  • Kidney allograft
  • Mixed hematopoietic chimerism
  • Nonmyeloablative conditioning regimen
  • Recipient lymphocyte infusion
  • Tolerance

ASJC Scopus subject areas

  • Transplantation

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