Activation‐induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance

@article{Pender1999ActivationinducedAO,
  title={Activation‐induced apoptosis of autoreactive and alloreactive T lymphocytes in the target organ as a major mechanism of tolerance},
  author={Michael P. Pender},
  journal={Immunology and Cell Biology},
  year={1999},
  volume={77}
}
  • M. Pender
  • Published 1 June 1999
  • Biology, Medicine
  • Immunology and Cell Biology
Normal individuals have mature T lymphocytes that are capable of reacting to self‐antigens and can be activated by cross‐reacting environmental antigens. The mechanism that maintains immune tolerance and prevents these activated autoreactive T cells from causing autoimmune disease is unclear. We have previously hypothesized that activation‐induced apoptosis of previously activated autoreactive T cells in the target organ is a major mechanism for maintaining tolerance. Here I review the current… 
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A model in which a peptide antigen covalently bound to MHC class II is expressed at low levels on all MHCclass II positive cells in mice suggests that blocking OX40 signaling in vivo specifically reduces inflammation induced by cytokines, suggesting that Ox40 may directly influence differentiation to effector function.
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Evidence suggests that phagocytosis of apoptotic cells by DCs can induce Tregs, a finding that has significant implications for the treatment of a variety of immune-mediated inflammatory disorders.
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It is demonstrated that Fas and Bcl-2 regulate different pathways of apoptosis that may serve distinct functions in lymphocyte homeostasis and in the maintenance of T cell tolerance.
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The involvement of Fas and Fas ligand in cell death, with particular reference to the T cell, and the mechanism(s) by which they induce cell death is described and the role of AICD in immune system homeostasis is discussed.
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Findings link regulation of FLIP protein levels with cell cycle progression and provide an explanation for the increase in TCR-induced apoptosis observed during the S phase of the cell cycle.
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