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Variable relationship between chimerism and tolerance after hematopoietic cell transplantation without
Zachary L Gleit1, Yasushi Fuchimoto, Kazuhiko Yamada
1Transplantation Biology Research Center, Massachusetts General Hospital/Harvard Medical School, Boston, MA, USA.
Transplantation
|December 20, 2002
Summary
This study shows a nonmyelosuppressive protocol can achieve stable mixed chimerism and tolerance in swine, even without thymic irradiation. However, macrochimerism alone doesn't guarantee tolerance, highlighting the importance of in vitro immune response assays for predicting transplant success.
Area of Science:
- Transplantation immunology
- Hematopoietic stem cell transplantation
- Immunosuppression
Background:
- Established a non-myelosuppressive mixed chimerism protocol for MHC-incompatible swine hematopoietic cell transplantation.
- Investigated outcomes with and without thymic irradiation in this protocol.
- Aimed to correlate long-term chimerism with stable transplant tolerance.
Purpose of the Study:
- Evaluate the efficacy of a non-myelosuppressive conditioning protocol for inducing mixed chimerism and tolerance.
- Determine the role of thymic irradiation in this protocol.
- Define the relationship between the level of chimerism and the development of stable tolerance.
Main Methods:
- Utilized in vivo T-cell depletion and varying degrees of thymic irradiation.
- Administered cyclosporine post-transplantation.
- Infused cytokine-mobilized donor hematopoietic cells.
- Assessed chimerism via flow cytometry and evaluated tolerance through in vitro assays and kidney transplantation.
Main Results:
- Stable chimerism was achieved in most recipients (26/35), irrespective of thymic irradiation.
- Kidney allografts were accepted without immunosuppression in tolerant chimeric swine.
- Some animals showed antidonor immune responses despite persistent donor cells, leading to graft rejection.
Conclusions:
- The non-myelosuppressive protocol effectively induces stable chimerism and tolerance, even without thymic irradiation.
- Macrochimerism does not always equate to stable tolerance.
- Absence of in vitro antidonor immune responses predicts successful renal allograft acceptance in this model.