Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft

Murad Y. Yunusov, Christian S. Kuhr, George E. Georges, William J. Hogan, Anna G. Taranova, Marina Lesnikova, Yang Soo Kim, Kraig Abrams, Billanna Hwang, George E. Sale, Barry Storer, Rainer Storb, Richard A. Nash

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

BACKGROUND. Donor-specific tolerance (DST) is induced after allogeneic hematopoietic cell transplantation (HCT) and is a potential strategy for prolonging survival of solid organ grafts. DST may persist in recipients with transient mixed hematopoietic chimerism (MC) when solid organ transplantation and HCT are done concomitantly. METHODS. In a canine model of allogeneic HCT after nonmyeloablative conditioning, DST to skin grafts was evaluated in dog leukocyte antigen (DLA)-identical recipients with stable MC (n=11), or after rejection of the hematopoietic cell (HC) graft (n=19). RESULTS. There was significant improvement in the survival of DLA-identical HC donor-derived skin grafts in recipients with MC compared to normal recipients (n=7; P<0.0001). However, HC donor-derived skin grafts in four recipients with MC developed an inflammatory reaction without skin graft loss. This may represent partial DST. Survival of DLA-identical HC donor-derived skin grafts was also significantly prolonged compared to normal recipients even when skin grafting was delayed until after rejection of the HC graft (P=0.002). An inflammatory reaction developed in all nine of the surviving HC donor-derived skin grafts in this group, but there was no graft loss at last follow-up (median, 30 [range, 9-84] weeks). An increased time to rejection of the hematopoietic graft was associated with prolonged survival of the subsequent skin graft (P=0.02). CONCLUSION. In a model of stable MC, DST to skin grafts may be complete or partial. Partial DST can persist after HC graft rejection even if solid organ transplantation is delayed. Further investigations are required to understand the mechanisms responsible for DST after allogeneic HCT.

Original languageEnglish (US)
Pages (from-to)629-637
Number of pages9
JournalTransplantation
Volume82
Issue number5
DOIs
StatePublished - Sep 2006

Keywords

  • Dog
  • Graft rejection
  • Hematopoietic cell transplantation
  • Mixed hematopoietic chimerism
  • Skin transplantation

ASJC Scopus subject areas

  • Transplantation

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    Yunusov, M. Y., Kuhr, C. S., Georges, G. E., Hogan, W. J., Taranova, A. G., Lesnikova, M., Kim, Y. S., Abrams, K., Hwang, B., Sale, G. E., Storer, B., Storb, R., & Nash, R. A. (2006). Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft. Transplantation, 82(5), 629-637. https://doi.org/10.1097/01.tp.0000229449.09622.28