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Related Experiment Videos

Tolerance induction in mature T lymphocytes

J Alferink1, A Tafuri, A Klevenz

  • 1Division of Molecular Immunology, German Cancer Research Center, Heidelberg, Germany.

Novartis Foundation Symposium
|October 7, 1998
PubMed
Summary

Healthy individuals possess self-reactive T cells, controlled by peripheral tolerance mechanisms. Adult mice showed tolerance induction is not possible for T cells newly exported from the thymus to keratinocyte antigens.

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Area of Science:

  • Immunology
  • Autoimmunity
  • T cell tolerance

Background:

  • Self-reactive T cells are present in healthy individuals, necessitating robust control mechanisms to prevent autoimmunity.
  • Peripheral tolerance is crucial for maintaining immune homeostasis and preventing self-attack.
  • Previous studies suggested continuous migration and tolerization of naive T cells in non-lymphoid tissues.

Purpose of the Study:

  • To investigate the potential for continuous tolerance induction of naive T cells in adult mice against antigens expressed on keratinocytes.
  • To determine if the adult physiological environment supports tolerance induction in newly thymic-exported T cells.

Main Methods:

  • Utilized double-transgenic mice (Des.TCR x 2.4Ker-Kb) expressing a foreign antigen (H-2Kb) exclusively outside the thymus.

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  • Generated chimeric mice (Des.TCR x 2.4Ker-Kb.Rag-2-) by crossing 2.4Ker-Kb mice with Rag-2-deficient mice and reconstituting with Des.TCR bone marrow cells.
  • Assessed tolerance by observing the presence and function of anti-Kb T cells in chimeric mice.

    • Main Results:

    • Tolerance was not observed in the chimeric adult mice (Des.TCR x 2.4Ker-Kb.Rag-2-).
    • This indicates that the adult physiological environment does not facilitate tolerance induction to keratinocyte-expressed antigens in newly exported T cells.
    • The findings suggest that regulatory mechanisms maintaining peripheral tolerance in adult Des.TCR x 2.4Ker-Kb animals are distinct from initial tolerance induction.

    Conclusions:

    • Unlike in neonates, the adult immune system does not readily induce tolerance to keratinocyte-expressed antigens in naive T cells emigrating from the thymus.
    • Peripheral tolerance in adult mice relies on regulatory events that maintain existing tolerance rather than de novo induction in non-lymphoid tissues.
    • These findings challenge the notion of continuous peripheral tolerization of naive T cells in adult non-lymphoid tissues.