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Related Experiment Videos

Tolerance through bone marrow transplantation with costimulation blockade.

Thomas Wekerle1, Peter Blaha, Felix Langer

  • 1Department of Surgery, Vienna General Hospital, Austria. thomas.wekerle@akh-wien.ac.at

Transplant Immunology
|August 16, 2002
PubMed
Summary
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Inducing transplant tolerance is challenging. New methods using costimulation blockade with bone marrow transplants show promise for less toxic mixed chimerism, potentially enabling clinical application.

Area of Science:

  • Immunology
  • Transplantation Biology
  • Cellular and Molecular Medicine

Background:

  • Achieving routine tolerance induction in organ transplant recipients remains a significant clinical challenge.
  • Allogeneic bone marrow transplantation (BMT) can induce donor-specific tolerance via mixed chimerism in experimental models.
  • Toxicity associated with host conditioning is a major limitation for clinical BMT.

Purpose of the Study:

  • To review the general principles of tolerance induction through BMT.
  • To describe recent advancements in BMT using costimulation blockade for mixed chimerism.
  • To discuss the mechanisms underlying tolerance induction with these novel regimens.

Main Methods:

  • Utilizing costimulation blocking reagents, such as anti-CD154 monoclonal antibodies and CTLA4Ig fusion protein.

Related Experiment Videos

  • Developing less toxic models of mixed chimerism, minimizing or eliminating host T cell depletion.
  • Employing high-dose BMT, sometimes in conjunction with costimulation blockade, to obviate cytoreductive conditioning.

    • Main Results:

    • Costimulation blockade has facilitated less toxic induction of mixed chimerism.
    • These approaches have reduced or eliminated the need for host T cell depletion and cytoreductive treatments.
    • Experimental models demonstrate robust donor-specific tolerance through these modified BMT strategies.

    Conclusions:

    • BMT with costimulation blockade offers a promising avenue for inducing transplant tolerance with reduced toxicity.
    • Further research is needed to address unresolved issues for successful clinical translation.
    • Identifying and overcoming barriers to clinical implementation is crucial for advancing this therapeutic approach.