title: Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft.
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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors.forename: Murad Y
authors.initials: MY
authors.lastname: Yunusov
authors.forename: Christian S
authors.initials: CS
authors.lastname: Kuhr
authors.forename: George E
authors.initials: GE
authors.lastname: Georges
authors.forename: William J
authors.initials: WJ
authors.lastname: Hogan
authors.forename: Anna G
authors.initials: AG
authors.lastname: Taranova
authors.forename: Marina
authors.initials: M
authors.lastname: Lesnikova
authors.forename: Yang-Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Kraig
authors.initials: K
authors.lastname: Abrams
authors.forename: Billanna
authors.initials: B
authors.lastname: Hwang
authors.forename: George E
authors.initials: GE
authors.lastname: Sale
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
mesh_terms: D000818:Animals; D004285:Dogs; D006084:Graft Rejection; D006085:Graft Survival; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D007108:Immune Tolerance; D007421:Intestine, Small / Q000637:transplantation; D023421:Models, Animal; D016038:Skin Transplantation / Q000276:immunology*; D014019:Tissue Donors; D014184:Transplantation, Homologous