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Publication : Surface T cell Fas receptor/CD95 regulation, in vivo activation, and apoptosis. Activation-induced death can occur without Fas receptor.

First Author  Tucek-Szabo CL Year  1996
Journal  J Immunol Volume  156
Issue  1 Pages  192-200
PubMed ID  8598462 Mgi Jnum  J:31074
Mgi Id  MGI:78544 Doi  10.4049/jimmunol.156.1.192
Citation  Tucek-Szabo CL, et al. (1996) Surface T cell Fas receptor/CD95 regulation, in vivo activation, and apoptosis. Activation-induced death can occur without Fas receptor. J Immunol 156(1):192-200
abstractText  Fas-mediated apoptosis is a form of cell death that operates through a receptor-ligand interaction. The FasR has been implicated directly in peripheral T cell tolerance and activation-induced apoptosis of T cells in vitro, although to date its expression on murine peripheral T cells has been characterized incompletely, In this study, we document substantial expression of FasR on the vast majority of recent thymic emigrants and resting peripheral T lymphocytes. FasR ligation can induce death in a minor (similar to 5%) subset of these cells, By contrast to rather slow activation-mediated FasR up- regulation in vitro, we demonstrate that in vivo T cell activation by alpha CD3 mAb or superantigen results in rapid up-regulation of the FasR. This up-regulation is paralleled by the kinetics of activation-induced apoptosis in lymph node T cells, However, we demonstrate that the FasR is not necessary for activation-induced cell death, Lymph node T cells from young, healthy, FasR expression- deficient MRL-lpr/lpr animals could be activated in vivo through the TCR-CD3 complex. Most importantly, MRL-lpr/lpr T cells underwent massive activation-induced apoptosis in response to high and intermediate doses of alpha CD3. At a low alpha CDS dose, however, both MRL-lpr/lpr and MRL+/+ T cells were activated similarly, but only the latter underwent adequate apoptosis. Taken together, these findings suggest that in vivo, the Fas pathway may not be the only regulator of activation-induced T cell death, but that this pathway may be critical in regulating responses to weak stimuli.
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