Regulation of cell surface expression of Fas (CD95) ligand and susceptibility to Fas (CD95)-mediated apoptosis in activation-induced T cell death involves calcineurin and protein kinase C, respectively

R. Tóth, Éva Szegezdi, Gábor Molnár, Janet M. Lord, L. Fésüs, Z. Szondy

Research output: Contribution to journalArticle

29 Citations (Scopus)

Abstract

We show that an influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP-12-7) enters the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR) stimulation. These cells express Fas and FasL mRNA, cell surface Fas and intracellular FasL, but do not enter apoptosis upon Fas ligation prior to TCR stimulation. TCR stimulation additionally results in protein synthesis-dependent cell surface expression of the preformed FasL. Addition of phorbol dibutyrate (PBu2) alone was sufficient to induce susceptibility to Fas ligation induced apoptosis, while addition of both PBu2 and calcium ionophore A23187 were required to induce FasL cell surface expression. Addition of cyclosporin A completely inhibited TCR-mediated death and FasL cell surface up-regulation, but had no effect on apoptosis induced directly by Fas ligation following TCR stimulation. Inhibitors of protein kinase C (PKC) (Go 6976 and GF 109203X) completely inhibited TCR-induced susceptibility to Fas ligation, but only partially inhibited TOP-induced cell surface expression of FasL. PKC isoenzymes α, β, δ and ζ were expressed by this cell line and only the α and βI isoforms translocated to the membrane fraction upon TCR stimulation. Our data suggest that in activation-induced T cell apoptosis PKC is involved in pathways that mediate the acquisition of Fas susceptibility, while calcineurin is required for cell surface expression of the preformed FasL.

Original languageEnglish
Pages (from-to)383-393
Number of pages11
JournalEuropean Journal of Immunology
Volume29
Issue number2
DOIs
Publication statusPublished - 1999

Fingerprint

Fas Ligand Protein
Calcineurin
Protein Kinase C
T-Cell Antigen Receptor
Cell Death
Apoptosis
T-Lymphocytes
Ligation
Calcium Ionophores
Calcimycin
Hybridomas
Hemagglutinins
Suicide
Human Influenza
Cyclosporine
Isoenzymes
Protein Isoforms
Up-Regulation
Cell Line
Messenger RNA

Keywords

  • Apoptosis
  • Fas
  • Fas ligand
  • Protein kinase C
  • T cell

ASJC Scopus subject areas

  • Immunology

Cite this

@article{bf7fd06c2989433499da4d527d8d8893,
title = "Regulation of cell surface expression of Fas (CD95) ligand and susceptibility to Fas (CD95)-mediated apoptosis in activation-induced T cell death involves calcineurin and protein kinase C, respectively",
abstract = "We show that an influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP-12-7) enters the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR) stimulation. These cells express Fas and FasL mRNA, cell surface Fas and intracellular FasL, but do not enter apoptosis upon Fas ligation prior to TCR stimulation. TCR stimulation additionally results in protein synthesis-dependent cell surface expression of the preformed FasL. Addition of phorbol dibutyrate (PBu2) alone was sufficient to induce susceptibility to Fas ligation induced apoptosis, while addition of both PBu2 and calcium ionophore A23187 were required to induce FasL cell surface expression. Addition of cyclosporin A completely inhibited TCR-mediated death and FasL cell surface up-regulation, but had no effect on apoptosis induced directly by Fas ligation following TCR stimulation. Inhibitors of protein kinase C (PKC) (Go 6976 and GF 109203X) completely inhibited TCR-induced susceptibility to Fas ligation, but only partially inhibited TOP-induced cell surface expression of FasL. PKC isoenzymes α, β, δ and ζ were expressed by this cell line and only the α and βI isoforms translocated to the membrane fraction upon TCR stimulation. Our data suggest that in activation-induced T cell apoptosis PKC is involved in pathways that mediate the acquisition of Fas susceptibility, while calcineurin is required for cell surface expression of the preformed FasL.",
keywords = "Apoptosis, Fas, Fas ligand, Protein kinase C, T cell",
author = "R. T{\'o}th and {\'E}va Szegezdi and G{\'a}bor Moln{\'a}r and Lord, {Janet M.} and L. F{\'e}s{\"u}s and Z. Szondy",
year = "1999",
doi = "10.1002/(SICI)1521-4141(199902)29:02<383::AID-IMMU383>3.0.CO;2-A",
language = "English",
volume = "29",
pages = "383--393",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "2",

}

TY - JOUR

T1 - Regulation of cell surface expression of Fas (CD95) ligand and susceptibility to Fas (CD95)-mediated apoptosis in activation-induced T cell death involves calcineurin and protein kinase C, respectively

AU - Tóth, R.

AU - Szegezdi, Éva

AU - Molnár, Gábor

AU - Lord, Janet M.

AU - Fésüs, L.

AU - Szondy, Z.

PY - 1999

Y1 - 1999

N2 - We show that an influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP-12-7) enters the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR) stimulation. These cells express Fas and FasL mRNA, cell surface Fas and intracellular FasL, but do not enter apoptosis upon Fas ligation prior to TCR stimulation. TCR stimulation additionally results in protein synthesis-dependent cell surface expression of the preformed FasL. Addition of phorbol dibutyrate (PBu2) alone was sufficient to induce susceptibility to Fas ligation induced apoptosis, while addition of both PBu2 and calcium ionophore A23187 were required to induce FasL cell surface expression. Addition of cyclosporin A completely inhibited TCR-mediated death and FasL cell surface up-regulation, but had no effect on apoptosis induced directly by Fas ligation following TCR stimulation. Inhibitors of protein kinase C (PKC) (Go 6976 and GF 109203X) completely inhibited TCR-induced susceptibility to Fas ligation, but only partially inhibited TOP-induced cell surface expression of FasL. PKC isoenzymes α, β, δ and ζ were expressed by this cell line and only the α and βI isoforms translocated to the membrane fraction upon TCR stimulation. Our data suggest that in activation-induced T cell apoptosis PKC is involved in pathways that mediate the acquisition of Fas susceptibility, while calcineurin is required for cell surface expression of the preformed FasL.

AB - We show that an influenza hemagglutinin-specific CD4+ murine T cell hybridoma (IP-12-7) enters the apoptotic suicide program via the Fas ligand (FasL)/Fas-mediated pathway upon T cell receptor (TCR) stimulation. These cells express Fas and FasL mRNA, cell surface Fas and intracellular FasL, but do not enter apoptosis upon Fas ligation prior to TCR stimulation. TCR stimulation additionally results in protein synthesis-dependent cell surface expression of the preformed FasL. Addition of phorbol dibutyrate (PBu2) alone was sufficient to induce susceptibility to Fas ligation induced apoptosis, while addition of both PBu2 and calcium ionophore A23187 were required to induce FasL cell surface expression. Addition of cyclosporin A completely inhibited TCR-mediated death and FasL cell surface up-regulation, but had no effect on apoptosis induced directly by Fas ligation following TCR stimulation. Inhibitors of protein kinase C (PKC) (Go 6976 and GF 109203X) completely inhibited TCR-induced susceptibility to Fas ligation, but only partially inhibited TOP-induced cell surface expression of FasL. PKC isoenzymes α, β, δ and ζ were expressed by this cell line and only the α and βI isoforms translocated to the membrane fraction upon TCR stimulation. Our data suggest that in activation-induced T cell apoptosis PKC is involved in pathways that mediate the acquisition of Fas susceptibility, while calcineurin is required for cell surface expression of the preformed FasL.

KW - Apoptosis

KW - Fas

KW - Fas ligand

KW - Protein kinase C

KW - T cell

UR - http://www.scopus.com/inward/record.url?scp=0344026230&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0344026230&partnerID=8YFLogxK

U2 - 10.1002/(SICI)1521-4141(199902)29:02<383::AID-IMMU383>3.0.CO;2-A

DO - 10.1002/(SICI)1521-4141(199902)29:02<383::AID-IMMU383>3.0.CO;2-A

M3 - Article

C2 - 10064053

AN - SCOPUS:0344026230

VL - 29

SP - 383

EP - 393

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 2

ER -