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Related Experiment Videos

The thymus and central tolerance.

H Kishimoto1, J Sprent

  • 1Department of Immunology, IMM4, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.

Clinical Immunology (Orlando, Fla.)
|March 24, 2000
PubMed
Summary
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T cell tolerance, crucial for preventing autoimmunity, is primarily established in the thymus via negative selection of autoreactive T cells. This process largely occurs in the medulla involving semimature T cells, Fas, and costimulatory molecules.

Area of Science:

  • Immunology
  • T cell biology
  • Autoimmunity

Background:

  • T cell tolerance prevents autoimmune diseases by eliminating self-reactive T cells.
  • Negative selection, a key tolerance mechanism, occurs during T cell differentiation in the thymus.

Purpose of the Study:

  • To review evidence on the location and cellular stage of negative selection in mice.
  • To discuss the molecular mechanisms regulating negative selection.

Main Methods:

  • Review of existing immunological research and data.
  • Analysis of T cell differentiation pathways.
  • Examination of molecular signaling in thymic selection.

Main Results:

  • Negative selection predominantly occurs in the thymic medulla.

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  • Semimature T cells are the primary population undergoing negative selection.
  • Fas and costimulatory molecules play significant roles, while certain cytokines inhibit the process.

    • Conclusions:

    • The thymic medulla is the main site for eliminating autoreactive T cells.
    • Understanding these mechanisms is vital for controlling autoimmune diseases.