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Measuring Composition of CD95 Death-Inducing Signaling Complex and Processing of Procaspase-8 in this Complex
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Actin integrity is indispensable for CD95/Fas-induced apoptosis of HIV-specific CD8+ T cells

Constantinos Petrovas1, Yvonne M Mueller, Guibin Yang

  • 1Department of Microbiology and Immunology, Institute for Molecular Medicine and Infectious Disease, Drexel University College of Medicine, Drexel University, 2900 Queen Lane, Philadelphia, PA 19129, USA.

Apoptosis : an International Journal on Programmed Cell Death
|September 25, 2007
PubMed

Insights

Filamentous (F) actin disruption inhibits CD95/Fas-induced apoptosis in HIV-specific CD8+ T cells. This finding reveals actin as a critical mediator, potentially aiding new HIV immune enhancement therapies.

Area of Science:

  • Immunology
  • Cell Biology
  • Virology

Background:

  • Mitochondria and Bcl-2-family molecules influence apoptosis sensitivity in HIV-specific CD8+ T cells.
  • The role of filamentous (F) actin in this process was previously unexplored.

Purpose of the Study:

  • To investigate the role of filamentous (F) actin in the apoptosis of HIV-specific CD8+ T cells.
  • To determine if actin disruption affects CD95/Fas-induced apoptosis and caspase-8 activation.

Main Methods:

  • Disruption of actin using cytochalasin D (cytD) or lantrunculin A.
  • Assessment of CD95/Fas-induced and spontaneous apoptosis in HIV-specific CD8+ T cells.
  • Analysis of CD95/Fas distribution and levels.
  • Measurement of caspase-8 activation following anti-CD95/Fas treatment.

Main Results:

  • Disruption of actin significantly reduced CD95/Fas-induced apoptosis but did not affect spontaneous apoptosis.
  • Actin disruption inhibited apoptosis independently of CD95/Fas levels/distribution and T cell differentiation status (CD38+ vs. CD38-).
  • Cytochalasin D treatment reduced caspase-8 activation induced by anti-CD95/Fas in HIV-specific CD8+ T cells.

Conclusions:

  • Filamentous (F) actin is a critical mediator of CD95/Fas-induced apoptosis in HIV-specific CD8+ T cells.
  • Actin's role in apoptosis is independent of T cell activation status.
  • Understanding these mechanisms may inform therapies to enhance the immune system in HIV infection.

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