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Specific tolerance induction and transplantation: a single-day protocol
A de Vries-van der Zwan1, A C Besseling, L P de Waal
1Department of Transplantation Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service, Amsterdam.
Blood
|April 1, 1997
Summary
This study shows a new single-day protocol for organ transplantation. It combines bone marrow transfusion with immediate skin grafting, achieving donor-specific tolerance and acceptance in mice, paving the way for clinical applications.
Area of Science:
- Immunology
- Transplantation Biology
- Hematopoietic Stem Cell Transplantation
Background:
- Mixed hematopoietic chimerism and donor-specific tolerance are induced by bone marrow transfusion in animal models.
- Clinical transplantation faces challenges due to the long interval between tolerance induction and organ transplantation.
- Simultaneous organ placement with bone marrow transfusion is crucial for clinical viability.
Purpose of the Study:
- To investigate a novel single-day protocol for inducing tolerance and chimerism for organ transplantation.
- To assess the feasibility of immediate allograft placement after conditioning and bone marrow transfusion.
Main Methods:
- Recipient mice underwent a conditioning regimen including anti-CD3, anti-CD4 antibodies, and low-dose total body irradiation (3-6 Gy).
- Mice received fully mismatched or haploidentical donor bone marrow cells.
- Skin transplantation was performed within 1 hour after conditioning and bone marrow infusion.
Main Results:
- Stable multilineage chimerism was achieved in recipient mice.
- Specific T-cell nonresponsiveness to donor antigens was observed.
- Donor skin grafts were accepted permanently, indicating successful tolerance induction.
Conclusions:
- A single-day protocol combining conditioning, bone marrow transfusion, and immediate allograft placement can induce stable chimerism and donor-specific tolerance.
- This protocol shows significant potential for clinical application in both cadaveric and living-related organ transplantation.
- The findings support the advancement of transplantation strategies by overcoming time constraints in tolerance induction.