Partial donor-specific tolerance to delayed skin grafts after rejection of hematopoietic cell graft.
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.
Yunusov
Murad Y
MY
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
Kuhr
Christian S
CS
Georges
George E
GE
Hogan
William J
WJ
Taranova
Anna G
AG
Lesnikova
Marina
M
Kim
Yang-Soo
YS
Abrams
Kraig
K
Hwang
Billanna
B
Sale
George E
GE
Storer
Barry
B
Storb
Rainer
R
Nash
Richard A
RA
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