Tolerance to vascularized kidney grafts in canine mixed hematopoietic chimeras.
BACKGROUND
Recent progress in allogeneic hematopoietic stem cell transplantation provides new methods for reliable engraftment with nonlethal conditioning regimens. These techniques have been successfully applied in the treatment of both malignant and nonmalignant diseases, but have not been fully exploited for their potential to tolerize recipients for organ transplantation. These studies were undertaken to test whether the tolerance of host immune cells toward donor hematopoietic cells in mixed hematopoietic chimeras extends to include a vascularized organ, the kidney.


METHODS
Using nonmyeloablative doses of total body irradiation, a short course of immunosuppression, and hematopoietic stem cells from marrow or peripheral blood sources, five dog lymphocyte antigen-identical canines were made to become stable mixed hematopoietic chimeras with no development of graft-versus-host disease or posttransplant lymphoproliferative disorder. Subsequently, renal transplantations were performed between stem cell donor and recipient littermates, and no additional immunosuppressive therapy was given after stem cell transplantation.


RESULTS
All mixed chimeric dogs demonstrate different, but stable, levels of donor peripheral blood lymphocyte and granulocyte chimerism. With follow-up of longer than 1 year, all of the mixed chimeric dogs (five/five) have excellent renal function with normal serum creatinines (<1.5 mg/dl) and no pathological evidence of rejection on biopsies.


CONCLUSIONS
In a major histocompatibility-matched model, minor antigen differences between donor and recipient are not sufficient to induce a host immune response to a vascularized kidney transplant in mixed hematopoietic chimeras.
Kuhr
Christian S
CS
Department of Surgery, Urology and Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA.
Allen
Margaret D
MD
Junghanss
Christian
C
Zaucha
Jan M
JM
Marsh
Christopher L
CL
Yunusov
Murad
M
Zellme
Eustacia
E
Little
Marie-Térèse
MT
Torok-Storb
Beverly
B
Storb
Rainer
R
D000818:Animals; D003404:Creatinine / Q000097:blood; D004285:Dogs; D018380:Hematopoietic Stem Cell Transplantation; D007668:Kidney / Q000473:pathology / Q000503:physiopathology; D016030:Kidney Transplantation; D012079:Renal Circulation; D013997:Time Factors; D014019:Tissue Donors; D018183:Transplantation Chimera; D023001:Transplantation Tolerance
D003404:Creatinine