Newly discovered role for Fas ligand in the cell-cycle arrest of CD4+ T cells.
Fas Ligand (FasL) can induce apoptosis of Fas-bearing cells. It is expressed on the cell surface of many tumor cells, immune-privileged tissues and activated lymphocytes. We report here that FasL can itself transduce signals, leading to cell-cycle arrest and cell death in CD4+ T cells. In vitro, FasL engagement inhibited CD4+ T-cell proliferation, cell-cycle progression, and IL-2 secretion. In vivo, FasL engagement prevented superantigen-mediated CD4+, but not CD8+, T-cell expansion. These findings demonstrate that FasL engagement regulates cell-cycle progression, and show that FasL engagement in vivo has a potent anti-inflammatory effect specific for CD4+ T cells.
Desbarats
J
J
Department of Medicine, University of Vermont College of Medicine, Burlington 05405, USA.
Duke
R C
RC
Newell
M K
MK
D000818:Animals; D017209:Apoptosis; D017252:CD3 Complex / Q000502:physiology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology*; D002453:Cell Cycle; D002478:Cells, Cultured; D053222:Fas Ligand Protein; D007376:Interleukin-2 / Q000096:biosynthesis; D008024:Ligands; D008562:Membrane Glycoproteins / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D015398:Signal Transduction; D019014:fas Receptor / Q000502:physiology*
D017252:CD3 Complex; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007376:Interleukin-2; D008024:Ligands; D008562:Membrane Glycoproteins; D019014:fas Receptor