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Apoptosis pp 179-200 | Cite as

Nuclear Receptors and Thymocyte Apoptosis: Shaping the Immune Repertoire

  • Melanie S. Vacchio
  • Yili Yang
  • Jonathan D. Ashwell
Part of the Pezcoller Foundation Symposia book series (PFSO, volume 5)

Abstract

Programmed cell death (PCD) plays a critical role in the generation of the antigen-specific immune repertoire. Both the T cell receptor (TCR) ligand-binding chains and immunoglobulin are generated randomly from the rearrangement of independent gene segments. While this process ensures the diversity of the immune cell receptor repertoire, it also results in the generation of T cells that express receptors that recognize self antigens in the context of self major histocompatibility complex (MHC)-encoded molecules with high affinity. The most effective way to deal with these potentially autoreactive cells is to eliminate them, a process referred to as “negative selection”. Deletion of potentially autoreactive T cells usually occurs in the thymus. Use of anti-TCR antibodies or bacterial superantigens (which mimic receptor occupancy by a natural ligand) during fetal thymic organ cultures results in PCD of immature CD4+ CD8+ thymocytes1,2, as does exposure of thymocytes from TCR-transgenic mice to the appropriate antigen3,4. The dying thymocytes manifest the classic apoptotic phenotype: membrane blebbing, cytoplasmic condensation, and chromatin clumping, accompanied by endonuclease-mediated cleavage of internucleosomal DNA1. Injection of cyclosporin A, which blocks activation-induced T cell hybridoma and thymocyte apoptosis5,6, prevents the deletion of a population of autoreactive T cells when the thymus regenerates after sublethal irradiation7,8.

Keywords

Retinoic Acid Negative Selection Thymic Epithelial Cell Thymocyte Apoptosis Steroid Receptor Expression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Melanie S. Vacchio
    • 1
  • Yili Yang
    • 1
  • Jonathan D. Ashwell
    • 1
  1. 1.Laboratory of Immune Cell Biology, Biological Response Modifiers ProgramNational Institutes of HealthBethesdaUSA

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