Korean J Hematol.
2002 Feb;37(1):46-53.
The Immune Tolerance Effect of Donor Chimerism Induced by Sublethal dose of Radiation on Allogeneic Organ Transplantation
- Affiliations
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- 1Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea. jak@vincent.cuk.ac.kr
- 2Hematopoietic Stem Cell Transplantation Laboratory, The Catholic University of Korea, Seoul, Korea.
- 3Plastic Surgery and Radiation Oncology, The Catholic University of Korea, Seoul, Korea.
Abstract
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BACKGROUND: Transplantation of solid organs has been increasing explosively. However, numerous problems remain unsolved, including the requirement for chronic immunosuppressive therapy and the shortage of donor organs. Recently one way to overcome this is bone marrow transplantation after total body irradiation. Especially though the dose of radiation used for conditioning is decreased, allogeneic bone marrow cells are engrafted and it can induce donor specific tolerance for allografting. The aim of this study is to develop a nonlethal conditioning approach to achieve donor chimerism and to confirm donor specific tolerance in C57BL/6 mice.
METHODS
We performed experiments on C57BL/6 mice divided into three groups according to preparatory radiation dosage. C57BL/6 mice received sublethal dose of radiation and transplanted with bone marrow cells from BALB/c. The percentage of donor derived cells was analyzed by flow cytometry (FACS) and the donor specific tolerance for allografts was assessed by BALB/c skin grafts and so did it by mixed lymphocyte reaction (MLR) and cytotoxicity (CML) using spleen cells from chimeras (BALB/c->C57BL/6).
RESULTS
Induction of alllogeneic donor chimerism occurred in 50%, 100%, 100% of animals irradiated with 6Gy, 7Gy, and 9Gy TBI, respectively. One hundred percent of chimeras with evidence of donor chimerism accepted skin allografts. Moreover, mixed chimeras exhibited donor specific tolerance in vitro as assessed by MLR and CML.
CONCLUSION
This strategy induced the donor chimerism and exhibited the donor specific tolerance effect for skin allografting.
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