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Induction of immunologic tolerance for transplantation
A A Rossini1, D L Greiner, J P Mordes
1Department of Medicine, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
Physiological Reviews
|January 29, 1999
Summary
Organ transplantation relies on immunosuppression, which carries risks like infection and cancer. Tolerance-based therapies, particularly donor-specific T-cell unresponsiveness, offer a promising alternative to lifelong immunosuppression for improved graft survival.
Area of Science:
- Immunology
- Transplantation Biology
- Medical Science
Background:
- Organ transplantation has become a vital treatment, enabled by advancements in understanding the immune system.
- Current immunosuppressive drugs, while effective, have significant toxicities and long-term risks, including infection, cancer, and graft dysfunction.
- Patients face a difficult choice between managing their illness and the side effects of lifelong immunosuppression.
Purpose of the Study:
- To review the fundamental biology, protocols, experimental outcomes, and clinical implications of tolerance-based transplantation.
- To explore strategies for inducing donor-specific T-cell unresponsiveness as an alternative to conventional immunosuppression.
- To highlight the potential of tolerance-based therapies for long-term graft survival without immunosuppression.
Main Methods:
- Review of existing literature on transplantation immunology and tolerance induction.
- Analysis of strategies such as graft modification, leukocyte removal, transplantation to privileged sites, and encapsulation.
- Focus on experimental and clinical data related to donor-specific T-cell unresponsiveness.
Main Results:
- Tolerance-based therapies, especially those inducing T-cell unresponsiveness, show significant promise for long-term graft survival.
- Recent studies suggest that achieving graft acceptance without immunosuppression is becoming a clinical reality.
- Donor-specific T-cell unresponsiveness is a key area of focus for developing effective tolerance-based strategies.
Conclusions:
- Tolerance-based transplantation represents a paradigm shift from lifelong immunosuppression.
- Inducing donor-specific T-cell unresponsiveness is a highly promising approach for future transplantation therapies.
- Tolerance-based strategies offer the potential to mitigate the risks associated with current immunosuppressive treatments, improving patient outcomes.