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Related Experiment Videos

Tolerance induction by thymic medullary epithelium.

M W Hoffmann1, J Allison, J F Miller

  • 1Walter and Eliza Hall Institute of Medical Research, Royal Melbourne Hospital, Victoria, Australia.

Proceedings of the National Academy of Sciences of the United States of America
|April 1, 1992
PubMed
Summary

Thymic medullary epithelium induces split tolerance. In vivo tolerance to foreign antigens occurs alongside strong in vitro T cell responses when interleukin 2 is present.

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Area of Science:

  • Immunology
  • Developmental Biology
  • Transplantation Immunology

Background:

  • The thymus is crucial for T cell development and immune tolerance.
  • Medullary thymic epithelium plays a key role in self-tolerance induction.
  • Understanding medullary thymic epithelium function is vital for controlling immune responses.

Purpose of the Study:

  • To investigate the role of thymic medullary epithelium in inducing immune tolerance.
  • To determine if medullary expression of an antigen is sufficient for tolerance induction.
  • To characterize the nature of tolerance induced by medullary thymic epithelium.

Main Methods:

  • Grafting of embryonic branchial clefts from E mu-Kb transgenic mice (expressing H-2Kb antigen) into athymic nude mice.

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  • Morphological and functional assessment of grafted thymic tissue.
  • In vivo skin graft assays to assess tolerance.
  • In vitro cytotoxicity assays and limiting-dilution analyses to evaluate T cell reactivity.

    • Main Results:

    • Grafts successfully differentiated into functional thymic tissue expressing H-2Kb.
    • Mice with H-2Kb expression in the medulla showed in vivo tolerance to H-2Kb disparate skin grafts.
    • In vitro assays revealed T cell reactivity to H-2Kb in the presence of interleukin 2.
    • Frequencies of T cells reactive to H-2Kb were similar to those reactive to third-party antigens.

    Conclusions:

    • Medullary thymic epithelium can induce a specific form of tolerance, termed 'split tolerance'.
    • Split tolerance involves in vivo unresponsiveness but preserved in vitro reactivity.
    • This finding highlights the complex mechanisms of T cell tolerance induction within the thymus.