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PMID: 9382892 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

T cell receptor signals enhance susceptibility to Fas-mediated apoptosis.

The Journal of experimental medicine ·Vol. 186 ·No. 11 ·1997-12-01 ·Pages 1939-44

Wong B, Arron J, Choi Y

Abstract

Fas(CD95) and its ligand (FasL) interaction plays a pivotal role in T cell receptor (TCR)-mediated apoptosis. However, the susceptibility of T cells to Fas-mediated apoptosis is tightly regulated during immune responses, a regulation which is thought to maintain the antigen-specificity of T cell apoptosis. Here we show that TCR stimulation enhances the induction of Fas-mediated apoptosis. In addition, using a mutant T cell hybridoma with impaired FasL expression, we show that the synergy provided by TCR stimulation can be mimicked by activators of PKC but not calcium influx. This effect cannot be inhibited by actinomycin D, suggesting that TCR stimulation leads to the alteration in preexisting signaling molecules to enhance Fas-mediated apoptosis. Our results therefore provide a mechanism of how Fas-FasL interactions lead to T cell death in an antigen-specific manner via repetitive antigen stimulation.

MeSH Terms
Animals Apoptosis/physiology Calcium/physiology Cyclosporine/pharmacology DNA-Binding Proteins/physiology Dactinomycin/pharmacology Drug Synergism Enzyme Activation/drug effects Fas Ligand Protein Hybridomas Immunosuppressive Agents/pharmacology Ionomycin/pharmacology Ionophores/pharmacology Membrane Glycoproteins/deficiency,genetics,physiology Mice Mice, Inbred BALB C Nuclear Receptor Subfamily 4, Group A, Member 1 Nucleic Acid Synthesis Inhibitors/pharmacology Protein Kinase C/physiology Receptors, Antigen, T-Cell/physiology Receptors, Cytoplasmic and Nuclear Receptors, Steroid Recombinant Fusion Proteins/immunology Signal Transduction Tetradecanoylphorbol Acetate/pharmacology Transcription Factors/physiology fas Receptor/physiology
Chemicals
DNA-Binding Proteins Fas Ligand Protein Fasl protein, mouse Immunosuppressive Agents Ionophores Membrane Glycoproteins Nr4a1 protein, mouse Nuclear Receptor Subfamily 4, Group A, Member 1 Nucleic Acid Synthesis Inhibitors Receptors, Antigen, T-Cell Receptors, Cytoplasmic and Nuclear Receptors, Steroid Recombinant Fusion Proteins Transcription Factors fas Receptor Dactinomycin Ionomycin Cyclosporine Protein Kinase C Tetradecanoylphorbol Acetate Calcium
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wong B
Howard Hughes Medical Institute, The Rockefeller University, New York 10021, USA.
Arron J
Choi Y
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33 references, click to expand
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Article Info
Journal
The Journal of experimental medicine
Abbr.
J Exp Med
ISSN
0022-1007
DOI
10.1084/jem.186.11.1939
Published
1997-12-01
Pages
1939-44
Language
English
Region
United States
NLM ID
2985109R
PMCID
PMC2199157
Subset
IM
Grants
NIAID NIH HHS · R01 AI/CA41082 · United States
External Links
PubMed source DOI: 10.1084/jem.186.11.1939 PMC Full Text View journal details
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