Delayed Induction of Mixed Chimerism Permits Kidney-Induced Cardiac Allograft Tolerance to be Applied to Recipients of Cadaveric Organs.
1Center for Transplantation Sciences, Department of Surgery, Massachusetts General Hospital, Boston, MA
2Department of Pathology, Massachusetts General Hospital, Boston, MA
3Department of Surgery, Massachusetts General Hospital, Boston, MA
4Division of Cardiac Surgery, Department of Surgery, Massachusetts General Hospital, Boston, MA.
Meeting: 2016 American Transplant Congress
Abstract number: 478
Keywords: Allorecognition, Immunogenicity, Primates, Stem cells
Session Information
Date: Tuesday, June 14, 2016
Session Name: Concurrent Session: Bone Marrow Transplantation and Chimerism: Animal Models
Session Time: 4:30pm-6:00pm
Presentation Time: 5:06pm-5:18pm
Location: Room 313
(BACKGROUND)
Cardiac tolerance in nonhuman primates (NHPs) has been induced for the first time by kidney co-transplantation in combination with donor bone marrow infusion when the conditioning protocol is started six days before transplantation. However, this strategy precludes the use of cadaveric donors. Here, we investigated whether delaying the induction of mixed chimerism until four months post heart and kidney co-transplantation would achieve the same stable state of tolerance.
(METHODS)
Allogeneic heart and kidneys from the same donor were co-transplanted in NHPs treated with tacrolimus, mycophenolate mofetil and methylprednisolone. After four months, immunosuppression was stopped and each recipient underwent bone marrow transplantation with frozen cells from the organ donor. They also received nonmyeloablative conditioning consisting of 3 Gy total body irradiation, 7 Gy local thymic irradiation, anti-thymocyte globulin, anti-CD154 mAb, anti-CD8 mAb and a 28 day course of cyclosporine. Control animals underwent the same treatment but received an isolated heart transplant.
(RESULTS)
Recipients of combined heart and kidney transplants (n=3) achieved long-term survival of both allografts (>547, >588, >1093 days) with no evidence of acute or chronic rejection. Remarkably, tolerance of the cardiac allograft was maintained in one recipient even after the donor kidney was removed. Delayed tolerance induction was associated with donor-specific T cell hypo-/unresponsiveness, the absence of alloantibodies, and the presence of Tregs in the accepted kidney. In contrast, recipients of isolated hearts demonstrated acute rejection in 48, 147, and 152 days.
(CONCLUSION)
Tolerance of MHC-mismatched hearts has been achieved in NHPs through kidney co-transplantation and the delayed induction of mixed hematopoietic chimerism. Delaying mixed chimerism conditioning until four months after heart and kidney co-transplantation permits this protocol to be applied to recipients of cadaveric heart and kidney allografts.
CITATION INFORMATION: Tonsho M, Benichou G, Yu R, Boskovic S, Colvin R, Farkash E, Smith R.-N, Allan J, Cosimi A, Kawai T, Madsen J. Delayed Induction of Mixed Chimerism Permits Kidney-Induced Cardiac Allograft Tolerance to be Applied to Recipients of Cadaveric Organs. Am J Transplant. 2016;16 (suppl 3).
To cite this abstract in AMA style:
Tonsho M, Benichou G, Yu R, Boskovic S, Colvin R, Farkash E, Smith R-N, Allan J, Cosimi A, Kawai T, Madsen J. Delayed Induction of Mixed Chimerism Permits Kidney-Induced Cardiac Allograft Tolerance to be Applied to Recipients of Cadaveric Organs. [abstract]. Am J Transplant. 2016; 16 (suppl 3). https://atcmeetingabstracts.com/abstract/delayed-induction-of-mixed-chimerism-permits-kidney-induced-cardiac-allograft-tolerance-to-be-applied-to-recipients-of-cadaveric-organs/. Accessed January 25, 2021.« Back to 2016 American Transplant Congress