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The requirements for Fas-associated death domain signaling in mature T cell activation and survival

Daniel R Beisner1, Isaac H Chu, Adrian F Arechiga

  • 1Molecular Biology Section, Division of Biological Sciences, University of California, San Diego, CA 92093, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|June 21, 2003
PubMed

Insights

Fas-associated death domain (FADD) is essential for T cell survival and proliferation. Blocking FADD signaling in T cells leads to cell death and impairs adaptive immunity, highlighting its critical role in immune responses.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Fas-associated death domain (FADD) is a cytoplasmic adapter molecule critical for apoptosis induction via death receptors.
  • FADD paradoxically also plays a vital role in T cell development and proliferation.

Purpose of the Study:

  • To investigate the role of FADD signaling in T cell activation, proliferation, and survival.
  • To determine the impact of FADD deficiency on adaptive immune responses in vivo.

Main Methods:

  • Utilized mice expressing a dominant-negative form of FADD (FADDdd) in T cells.
  • Assessed T cell activation, proliferation, and apoptosis following anti-TCR antibody stimulation and costimulation or cytokine treatment.
  • Analyzed adaptive immune responses in FADDdd-expressing mice infected with lymphocytic choriomenigitis virus.

Main Results:

  • T cell activation and proliferation were profoundly diminished in FADDdd-expressing T cells.
  • Blocking FADD signaling resulted in a high rate of T cell death during cell division, particularly in CD8 T cells.
  • FADDdd-expressing mice failed to mount an antigen-specific immune response upon viral infection.

Conclusions:

  • FADD signaling is indispensable for T cell survival and proliferation, balancing apoptosis and survival signals.
  • The proper functioning of FADD is crucial for mounting effective adaptive immune responses.
  • Caspaes, likely regulated by FADD, play a key role in determining T cell fate, impacting adaptive immunity.

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