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Durable mixed allogeneic chimerism and tolerance by a nonlethal radiation-based cytoreductive approach
1Department of Surgery, University of Pittsburgh, PA 15261, USA.
Journal of Immunology (Baltimore, Md. : 1950)
|October 1, 1996
Summary
This study shows a new method using antilymphocyte globulin and reduced irradiation to achieve bone marrow chimerism, enabling donor-specific tolerance for transplants with less toxicity.
Area of Science:
- Immunology
- Transplantation Biology
- Hematopoietic Stem Cell Transplantation
Background:
- Hemopoietic chimerism induces donor-specific tolerance for allografts.
- Lethal conditioning toxicity limits clinical application of bone marrow chimerism.
- Previous work showed reduced irradiation (700 cGy) and cyclophosphamide (CyP) improve engraftment.
Purpose of the Study:
- To develop a less toxic conditioning regimen for inducing hemopoietic chimerism and donor-specific tolerance.
- To evaluate the efficacy of antilymphocyte globulin (ALG) combined with TBI/CyP conditioning.
Main Methods:
- Mice received ALG, 300 cGy total body irradiation (TBI), and bone marrow (BM) transplantation, followed by CyP.
- Flow cytometry analyzed peripheral blood and bone marrow cell populations.
- Skin grafts and in vitro assays assessed donor-specific tolerance.
Main Results:
- ALG, TBI, and CyP conditioning achieved high rates (97%) of donor chimerism with reduced TBI (< or = 300 cGy).
- ALG depleted host T and NK cells, while CyP delayed thymocyte repopulation.
- Chimeric mice demonstrated stable multilineage chimerism and donor-specific tolerance.
Conclusions:
- This reduced-intensity conditioning regimen effectively induces hemopoietic chimerism and donor-specific tolerance.
- The model offers a potentially clinically applicable approach for transplantation tolerance.
- This method minimizes conditioning toxicity compared to traditional approaches.