Stimulation of CD95 (Fas) Blocks T Lymphocyte Calcium Channels through Sphingomyelinase and Sphingolipids

Calcium influx through store-operated calcium release-activated calcium channels (CRAC) is required for T cell activation, cytokine synthesis, and proliferation. The CD95 (Apo-1/Fas) receptor plays a role in self-tolerance and tumor immune escape, and it mediates apoptosis in activated T cells. In t...

Full description

Saved in:
Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 1999-11, Vol.96 (24), p.13795-13800
Main Authors: Lepple-Wienhues, Albrecht, Belka, Claus, Laun, Tilmann, Jekle, Andreas, Walter, Birgit, Wieland, Ulrich, Welz, Martina, Heil, Luzia, Kun, Jutta, Busch, Gillian, Weller, Michael, Bamberg, Michael, Gulbins, Erich, Lang, Florian
Format: Article
Language:English
Subjects:
Animals
Apoptosis
B lymphocytes
Biological Sciences
Calcium
Calcium - metabolism
Calcium Channel Blockers
calcium channels
Calcium Channels - metabolism
calcium influx
Calcium Signaling
CD95 antigen
Cell lines
Cells
Cellular biology
Ceramides
Ceramides - metabolism
fas Receptor - metabolism
Humans
Jurkat Cells
Lymphatic system
Lymphocyte Activation
Lymphocytes
Mast cells
Mice
Mice, Inbred C57BL
Receptors
sphingolipids
Sphingolipids - metabolism
Sphingomyelin Phosphodiesterase - metabolism
sphingomyelinase
T cell antigen receptors
T lymphocytes
T-Lymphocytes - metabolism
Tumor Cells, Cultured
Tumors
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Calcium influx through store-operated calcium release-activated calcium channels (CRAC) is required for T cell activation, cytokine synthesis, and proliferation. The CD95 (Apo-1/Fas) receptor plays a role in self-tolerance and tumor immune escape, and it mediates apoptosis in activated T cells. In this paper we show that CD95-stimulation blocks CRAC and Ca2+ influx in lymphocytes through the activation of acidic sphingomyelinase (ASM) and ceramide release. The block of Ca2+ entry is lacking in CD95-defective Ipr lymphocytes as well as in ASM-defective cells and can be restored by retransfection of ASM. C2 ceramide, C6 ceramide, and sphingosine block CRAC reversibly, whereas the inactive dihydroceramide has no effect. CD95-stimulation or the addition of ceramide prevents store-operated Ca2+ influx, activation of the transcriptional regulator NFAT, and IL-2 synthesis. The block of CRAC by sphingomyelinase metabolites adds a function to the repertoire of the CD95 receptor inhibiting T cell activation signals.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.96.24.13795