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 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 (approximately 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-Ipr/Ipr and animals could be activated in vivo through the TCR-CD3 complex. Most importantly, MRL-Ipr/Ipr T cells underwent massive activation-induced apoptosis in response to high and intermediate doses of alpha CD3. At a low alpha CD3 dose, however, both MRL-Ipr/Ipr 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.
Tucek-Szabo
C L
CL
Specialized Center of Research (SCOR), Memorial Sloan-Kettering Cancer Center, New York USA.
Andjelić
S
S
Lacy
E
E
Elkon
K B
KB
Nikolić-Zugić
J
J
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D017252:CD3 Complex / Q000276:immunology; D016923:Cell Death / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D053222:Fas Ligand Protein; D007399:Interphase / Q000276:immunology; D008198:Lymph Nodes / Q000166:cytology; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D008817:Mice, Mutant Strains; D017260:Receptor-CD3 Complex, Antigen, T-Cell / Q000276:immunology; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D015854:Up-Regulation / Q000276:immunology; D019014:fas Receptor / Q000502:physiology*
D017252:CD3 Complex; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D017260:Receptor-CD3 Complex, Antigen, T-Cell; D019014:fas Receptor