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MAPK/ERK signaling in activated T cells inhibits CD95/Fas-mediated apoptosis downstream of DISC assembly

T H Holmström1, I Schmitz, T S Söderström

  • 1Turku Centre for Biotechnology, University of Turku and Abo Akademi University, PO Box 123, FIN-20521 Turku, Finland.

The EMBO Journal
|October 18, 2000
PubMed

Insights

Mitogen-activated protein kinase (MAPK) signaling suppresses CD95-mediated apoptosis in activated T cells, preventing their elimination. This MAPK pathway activation inhibits key apoptotic proteins, prolonging T cell persistence during immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Activated T cells express CD95 ligand to induce apoptosis and self-eliminate.
  • Mitogen-activated protein kinase (MAPK) signaling is known to suppress CD95-mediated apoptosis in various cell types.

Purpose of the Study:

  • To investigate if MAPK signaling regulates T cell persistence and CD95-mediated apoptosis termination in activated T cells.
  • To elucidate the mechanism by which MAPK signaling influences CD95-mediated apoptosis during T cell activation.

Main Methods:

  • Activation of Jurkat T cells via the T cell receptor.
  • Analysis of MAPK signaling pathway activation.
  • Assessment of caspase-8 and Bid activation.
  • Evaluation of death-inducing signaling complex (DISC) assembly.
  • Experiments with activated primary peripheral T cells.

Main Results:

  • T cell receptor activation of Jurkat T cells rapidly suppresses CD95-mediated apoptosis through MAPK activation.
  • MAPK activation inhibits caspase-8 and Bid activation but does not affect DISC assembly.
  • Activated primary peripheral T cells become sensitive to CD95-mediated apoptosis upon MAPK signaling inhibition.

Conclusions:

  • MAPK signaling mediates the resistance of activated T cells to CD95-mediated apoptosis during the early phase of immune response.
  • MAPK activation appears to redirect DISC signaling, preventing caspase-8 and Bid activation.
  • Inhibition of MAPK signaling in primary T cells sensitizes them to CD95-mediated apoptosis, highlighting the pathway's physiological relevance.

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