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Related Experiment Videos

Toward tolerance: lessons learned from liver transplantation.

J J Fung1

  • 1Thomas E. Starzl Transplantation Institute, University of Pittsburgh, PA 15213, USA.

Liver Transplantation and Surgery : Official Publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
|August 4, 1999
PubMed
Summary

Achieving transplantation tolerance involves understanding its immunological, clinical, and outcome-based definitions. Research explores mechanisms like central and peripheral tolerance, and methods such as macrochimerism and T-cell costimulatory blockade to induce unresponsiveness to donor antigens.

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Area of Science:

  • Immunology
  • Transplantation Science
  • Cellular Biology

Background:

  • Transplantation tolerance is defined by immunological unresponsiveness to donor antigens, clinical ability to discontinue immunosuppression, and outcome-based prevention of chronic rejection.
  • Understanding the mechanisms of tolerance, including central and peripheral tolerance pathways, is crucial for advancing transplant outcomes.

Purpose of the Study:

  • To define the multifaceted concepts of transplantation tolerance.
  • To elucidate the various mechanisms involved in developing transplantation tolerance.
  • To review methods for achieving transplantation tolerance and discuss current limitations.

Main Methods:

  • Exploration of central tolerance (e.g., clonal deletion) and peripheral tolerance (e.g., blocking antibodies, T-cell anergy).

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  • Review of methods including macrochimerism (recipient cytoablation and donor reconstitution), microchimerism (bone marrow augmentation), intrathymic inoculation, and T-cell costimulatory blockade.
  • Analysis of limitations such as lack of tolerance markers and incomplete understanding of rejection mechanisms.

    • Main Results:

    • Tolerance can be conceptualized immunologically, clinically, and based on long-term outcomes.
    • Mechanisms involve both central and peripheral immune system regulation.
    • Various methods show promise but face limitations in defining and achieving stable tolerance.

    Conclusions:

    • Achieving transplantation tolerance requires a comprehensive understanding of its definitions and underlying mechanisms.
    • Current methods like T-cell costimulatory blockade offer potential but require further research.
    • Addressing limitations in defining tolerance and understanding rejection is essential for future advancements, possibly necessitating a two-pronged approach.