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Identification of Mediators of T-cell Receptor Signaling via the Screening of Chemical Inhibitor Libraries
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Caspase-3/CPP32-like activity is not sufficient to mediate apoptosis in an IL-2 dependent T cell line

J P Vasilakos1, T Lynch, T Ghayur

  • 1Department of Cell Biology, Parke-Davis Pharmaceutical Research Company, Division of Warner-Lambert, Ann Arbor, MI 48105, USA.

Apoptosis : an International Journal on Programmed Cell Death
|January 1, 1997
PubMed

Insights

Growth factor starvation induces T cell apoptosis, involving the caspase family. However, increased caspase-3/CPP32-like activity alone is insufficient to mediate this IL-2 starvation-induced cell death.

Area of Science:

  • Immunology
  • Cell Biology
  • Molecular Biology

Background:

  • Interleukin-2 (IL-2) is crucial for T cell survival, and its absence triggers apoptosis.
  • The IL-1beta-converting-enzyme (ICE)/caspase family is implicated in various apoptotic pathways.
  • Previous studies showed increased ICE/caspase-1 expression during T cell apoptosis, but ICE inhibition did not prevent cell death.

Purpose of the Study:

  • To investigate the role of other caspase family members in T cell apoptosis induced by growth factor deprivation.
  • To determine if elevated caspase-3/CPP32-like activity is sufficient to cause apoptosis upon IL-2 starvation.

Main Methods:

  • Measuring cytosolic CPP32-like activity via DEVD-pNA cleavage and poly(ADP-ribose) polymerase (PARP) cleavage in CTLL cells undergoing apoptosis.
  • Utilizing broad-spectrum (D-FMK) and specific (VAD-FMK, DEVD-FMK) ICE family inhibitors to assess their effect on CPP32-like activity and apoptosis.

Main Results:

  • Cytosolic CPP32-like activity and PARP cleavage increased during apoptosis following IL-2 deprivation.
  • Broad-spectrum ICE inhibitor (D-FMK) inhibited apoptosis, while specific inhibitors (VAD-FMK, DEVD-FMK) did not, despite inhibiting CPP32-like activity.
  • Increased CPP32-like activity was observed but was not sufficient to induce apoptosis in the absence of IL-2.

Conclusions:

  • The caspase family is involved in T cell apoptosis triggered by growth factor starvation.
  • Elevated caspase-3/CPP32-like activity is a consequence, not the sole mediator, of IL-2 starvation-induced T cell apoptosis.
  • Specific caspase members beyond ICE/caspase-1 may play a role, but their precise function in this context requires further investigation.

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