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Related Experiment Videos

Conventional immunosuppression is compatible with costimulation blockade-based, mixed chimerism tolerance induction.

Andrew B Adams1, Nozomu Shirasugi, Thomas R Jones

  • 1The Emory Transplant Center and Department of Surgery, Emory University School of Medicine, Atlanta, GA, USA.

American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons
|June 20, 2003
PubMed
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Combining T-cell costimulation blockade with conventional immunosuppressants, like calcineurin inhibitors, effectively induces donor-specific transplant tolerance. This strategy supports safe integration into clinical trials for preventing allograft rejection.

Area of Science:

  • Immunology
  • Transplantation Biology
  • Cellular and Molecular Medicine

Background:

  • T-cell costimulatory blockade is a promising strategy for preventing allograft rejection.
  • Previous research indicates that certain immunosuppressants can interfere with costimulation blockade efficacy.
  • Compatibility of various immunosuppressive agents with costimulation blockade needs evaluation for clinical application.

Purpose of the Study:

  • To assess the compatibility of different immunosuppressive agents with a costimulation blockade-based mixed chimerism tolerance protocol.
  • To determine if conventional immunosuppressants negate the benefits of costimulation blockade in tolerance induction.

Main Methods:

  • Mice were subjected to a mixed chimerism tolerance protocol incorporating T-cell costimulation blockade.

Related Experiment Videos

  • Various conventional immunosuppressive agents, including calcineurin inhibitors, were administered concurrently.
  • Assessment of multilineage macrochimerism, allograft acceptance, T-cell receptor utilization, and donor-specific tolerance was performed.

    • Main Results:

    • The addition of conventional immunosuppressants did not impede tolerance induction.
    • All treated mice achieved multilineage macrochimerism and accepted donor allografts.
    • Selective deletion of donor-reactive T cells was observed, confirming donor-specific tolerance upon challenge.

    Conclusions:

    • Conventional immunosuppressive agents, including calcineurin inhibitors, can be safely combined with costimulation blockade in a mixed chimerism strategy.
    • This combination approach supports the development of donor-specific transplant tolerance without compromising the efficacy of costimulation blockade.
    • Findings suggest these agents can be safely incorporated into clinical trials for nonmyelosuppressive, mixed chimerism-based tolerance strategies.