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Mechanisms of Lymphocyte Activation and Immune Regulation VI pp 241–262Cite as

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

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Part of the book series: Advances in Experimental Medicine and Biology ((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).

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Authors and Affiliations

  1. Department of Medicine Division of Clinical Immunology and Rheumatology, University of Alabama at Birmingham, Birmingham, Alabama, 35294, USA

    John D. Mountz, Jianhua Cheng, Pingar Yang, Zheng Wang, Changdan Liu, Xiao Su & Tong Zhou

  2. The Birmingham Veterans Administration Medical Center, Birmingham, Alabama, 35233, USA

    John D. Mountz & Jianhua Cheng

  3. Department of Inflammation, Amgen Boulder, Inc., Boulder, CO, 80301, USA

    Carl K. Edwards III

  4. Pharmaceutical Research Gene Technologies, F. Hoffmann-LaRoche, Ltd., Basel, Switzerland

    Horst Bluethmann

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  1. University of California, Irvine, Irvine, California, USA

    Sudhir Gupta

  2. University of Colorado Health Sciences Center, Denver, Colorado, USA

    J. John Cohen

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© 1996 Springer Science+Business Media New York

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Mountz, J.D. et al. (1996). Autoimmunity Due to Defective NUR77, Fas, and TNF-RI Apoptosis. In: Gupta, S., Cohen, J.J. (eds) Mechanisms of Lymphocyte Activation and Immune Regulation VI. Advances in Experimental Medicine and Biology, vol 406. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-0274-0_25

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  • DOI: https://doi.org/10.1007/978-1-4899-0274-0_25

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4899-0276-4

  • Online ISBN: 978-1-4899-0274-0

  • eBook Packages: Springer Book Archive

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