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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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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