IL-1β Convertase (ICE) Does Not Play a Requisite Role in Apoptosis Induced in T Lymphoblasts by Fas-Dependent or Fas-Independent CTL Effector Mechanisms

Donald J. Smith, Michael J. McGuire, Michael J. Tocci, Dwain L Thiele

Research output: Contribution to journalArticlepeer-review

42 Scopus citations

Abstract

Both IL-1β convertase (ICE) and other members of the ICE-like family of proteases have been reported to play a role in Fas-mediated apoptosis. Con A-stimulated T lymphoblasts generated from splenocytes isolated from ICE-deficient H-2b mice were found to be more susceptible than wild-type lymphoblasts to DNA fragmentation induced by H-2b-specific CTL derived from normal or Fas ligand-deficient gld/gld mice. Trinitrophenyl (TNP)-modified, H-2b target cell-specific CTL were generated from perforin-deficient mice and were found to induce DNA fragmentation only in target cells expressing functional Fas receptors. Similar rates of DNA fragmentation were induced in TNP-modified ICE -/- and ICE +/+ T lymphoblast targets by oerforin -/- TNP-modified, H-2b target cell-specific CTL. In addition, anti-Fas Abs induced apoptosis in thymocytes, Con A-stimulated spleen T cells, LPS-stimulated spleen B cells, and thymocytes from ICE -/- mice. However, DNA fragmentation induced by either allospecific FasL-defective CTL, or by perforin-deficient, TNP-modified, H-2b target cell-specific CTL was prevented in ICE -/- target cells loaded by electroporation with Ac-DEVD-CHO, an inhibitor of CPP32 and related ICE family proteases. These findings indicate that ICE does not play a requisite role in Fas-dependent or Fas-independent mechanisms of apoptosis induced in peripheral T lymphoblasts by CTL. However, both major pathways of CTL-induced apoptosis appear to be dependent on the enzymatic activity of other ICE family proteases.

Original languageEnglish (US)
Pages (from-to)163-170
Number of pages8
JournalJournal of Immunology
Volume158
Issue number1
StatePublished - Jan 1 1997

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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