SURFACE T-CELL FAS RECEPTOR CD95 REGULATION, IN-VIVO ACTIVATION, AND APOPTOSIS - ACTIVATION-INDUCED DEATH CAN OCCUR WITHOUT FAS RECEPTOR

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 cel ls in vitro, although to date its expression on murine peripheral T ce lls has been characterized incompletely, In this study, we document su bstantial expression of FasR on the vast majority of recent thymic emi grants 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 demon strate that in vivo T cell activation by alpha CD3 mAb or superantigen results in rapid up-regulation of the FasR. This up-regulation is par alleled by the kinetics of activation-induced apoptosis in lymph node T cells, However, we demonstrate that the FasR is not necessary for ac tivation-induced cell death, Lymph node T cells from young, healthy, F asR expression-deficient MRL-lpr/lpr animals could be activated in viv o through the TCR-CD3 complex. Most importantly, MRL-lpr/lpr T cells u nderwent massive activation-induced apoptosis in response to high and intermediate doses of alpha CD3. At a low alpha CDS dose, however, bot h MRL-lpr/lpr and MRL+/+ T cells were activated similarly, but only th e 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 critica l in regulating responses to weak stimuli.