Ligand-independent redistribution of Fas (CD95) into lipid rafts mediates clonotypic T cell death

Muppidi JR and Siegel RM
Source: Nat Immunol
Publication Date: (2004)
Issue: 5(2): 182-189
Research Area:
Immunotherapy / Hematology
Cells used in publication:
T cell, human stim.
Species: human
Tissue Origin: blood
In order to determine T cell sensitivity to FasL after T-cell receptor (TCR) restimulation, activated human CD4+ cells, derived from primary peripheral blood lymphocytes, were nucleofected with both a FasL and a GFP expression vector. It was shown that TCR-driven translocation of Fas into lipid rafts sensitizes cells to apoptosis mediated by T cell-derived FasL.
Clonotypic elimination of activated T cells through Fas-Fas ligand (CD95-CD95L) interactions is one mechanism of peripheral self-tolerance. T cell receptor (TCR) stimuli trigger FasL synthesis but also sensitize activated T cells to Fas-mediated apoptosis through an unknown mechanism. Here we show that TCR restimulation of activated human CD4(+) T cells resulted in Fas translocation into lipid raft microdomains before binding FasL, rendering these cells sensitive to apoptosis after stimulation with bivalent antibody or FasL. Disruption of lipid rafts reduced sensitivity to Fas-mediated apoptosis after TCR restimulation. Thus, the redistribution of Fas and other tumor necrosis factor family receptors into and out of lipid rafts may dynamically regulate the efficiency and outcomes of signaling by these receptors.