IL-1 beta convertase (ICE) does not play a requisite role in apoptosis induced in T lymphoblasts by Fas-dependent or Fas-independent CTL effector mechanisms.
Both IL-1beta 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 perforin -/- 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.
Smith
D J
DJ
Immunology Graduate Program, The University of Texas Southwestern Medical Center at Dallas, 75235, USA.
McGuire
M J
MJ
Tocci
M J
MJ
Thiele
D L
DL
D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D020170:Caspase 1; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000172:deficiency / Q000494:pharmacology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004792:Enzyme Precursors / Q000494:pharmacology; D006412:Hematopoietic Stem Cells / Q000187:drug effects / Q000276:immunology*; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D018345:Mice, Knockout; D009842:Oligopeptides / Q000494:pharmacology; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013601:T-Lymphocytes / Q000187:drug effects; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D019014:fas Receptor / Q000494:pharmacology*
D015853:Cysteine Proteinase Inhibitors; D004792:Enzyme Precursors; D008562:Membrane Glycoproteins; D009842:Oligopeptides; D052899:Pore Forming Cytotoxic Proteins; C099158:acetyl-aspartyl-glutamyl-valyl-aspartal; D019014:fas Receptor; D054353:Perforin; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D020170:Caspase 1