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Related Experiment Videos

Transplant tolerance: models, concepts and facts.

Nicola J Monk1, Roseanna E G Hargreaves, Elizabeth Simpson

  • 1Department of Nephrology & Transplantation, King's College, Guy's, King's and St Thomas' Medical School, 5th Floor TGH, Guy's Hospital, London, UK.

Journal of Molecular Medicine (Berlin, Germany)
|February 28, 2006
PubMed
Summary

Achieving transplant tolerance is challenging because T cells need survival signals to avoid death and become memory cells. Current strategies may fail due to the strong immune response in clinical transplantation.

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Area of Science:

  • Immunology
  • Transplantation Biology

Background:

  • Immunological tolerance to self-antigens and allogeneic transplants remains incompletely understood.
  • Co-stimulation blockade is a leading strategy for inducing transplant tolerance, but recent findings suggest T cell depletion may be the primary mechanism.

Purpose of the Study:

  • To re-evaluate the role of co-stimulation blockade in transplant tolerance.
  • To propose a new conceptual framework for understanding immunological tolerance.

Main Methods:

  • Review of existing literature on T cell activation, survival, and co-stimulation blockade.
  • Analysis of T cell death pathways and their role in tolerance induction.
  • Comparison of rodent models with clinical transplantation scenarios.

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Main Results:

  • Activated T cells require survival signals (cytokines) to prevent programmed cell death.
  • Failure of T cells to survive activation and develop into memory cells can lead to deletional tolerance.
  • Rodent models with weak alloresponses are more amenable to tolerance induction than clinical transplantation with strong alloresponses.

Conclusions:

  • Tolerance may represent a failure of T cells to survive activation and develop into memory cells.
  • The strength of the alloresponse and graft immunogenicity are critical factors in achieving tolerance.
  • Clinical transplantation's strong alloresponse poses significant challenges for current tolerance-inducing strategies.