Autoimmunity Due to Defective NUR77, Fas, and TNF-RI Apoptosis

  • John D. Mountz
  • Carl K. EdwardsIII
  • Jianhua Cheng
  • Pingar Yang
  • Zheng Wang
  • Changdan Liu
  • Xiao Su
  • Horst Bluethmann
  • Tong Zhou
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 406)

Abstract

Several molecules and pathways known to be of importance in apoptosis have been described in the thymus; however, their contribution to clonal deletion and tolerance induction remains controversial1–4. Although knockout of p53 leads to decreased sensitivity of murine thymocytes to radiation-induced apoptosis, negative selection remains intact5–7. Fas is a cell surface receptor that mediates apoptosis by interaction with a specific ligand and is expressed on most murine thymocytes8–11. Although mutant Fas antigen and Fas ligand cause autoimmune disease in 1pr/lpr and gld/gld mice, respectively10–12 no major negative selection defects have been found in Ipr/lpr mice13–17. Therefore, it is unlikely that Fas antigen is directly involved in negative selection in the thymus, but may be involved in apoptosis during early T cell development in the thymus. We have previously proposed that Fas expression duirng early thymocyte development plays a role in positive selection or pre-positive selection of thymocytes (Figure 1).

Keywords

Negative Selection Double Positive Thymocyte Apoptosis Double Positive Thymocyte Transgenic Male Mouse 
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 1996

Authors and Affiliations

  • John D. Mountz
    • 1
    • 2
  • Carl K. EdwardsIII
    • 3
  • Jianhua Cheng
    • 1
    • 2
  • Pingar Yang
    • 1
  • Zheng Wang
    • 1
  • Changdan Liu
    • 1
  • Xiao Su
    • 1
  • Horst Bluethmann
    • 4
  • Tong Zhou
    • 1
  1. 1.Department of Medicine Division of Clinical Immunology and RheumatologyUniversity of Alabama at BirminghamBirminghamUSA
  2. 2.The Birmingham Veterans Administration Medical CenterBirminghamUSA
  3. 3.Department of InflammationAmgen Boulder, Inc.BoulderUSA
  4. 4.Pharmaceutical Research Gene TechnologiesF. Hoffmann-LaRoche, Ltd.BaselSwitzerland

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