Do CTL kill target cells by inducing apoptosis?
Inhibitors of ICE-family proteases (caspases) block many examples of apoptotic cell death in vivo and in vitro, including multiple apoptotic stimuli for T lymphocytes. We have tested whether cell death induced by cytotoxic T lymphocytes was also blocked by caspase inhibitors. We found that the rapid apoptotic target cell death induced by Fas ligand-bearing CTL using the target Fas death pathway was efficiently blocked by caspase inhibitors. In contrast, target lysis induced by the CTL granule exocytosis pathway is not detectably blocked by such inhibitors, although the accompanying apoptotic nuclear damage is efficiently blocked. Thus caspase inhibitors prevent the hallmark phenotype of apoptosis without measurably affecting target cell death as evidenced by lysis.
Henkart
P A
PA
Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1360, USA.
Williams
M S
MS
Zacharchuk
C M
CM
Sarin
A
A
D000818:Animals; D017209:Apoptosis; D029742:Caenorhabditis elegans Proteins; D053148:Caspase 3; D020169:Caspases; D015550:Cell Degranulation; D003546:Cysteine Endopeptidases / Q000502:physiology*; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D053804:Granzymes; D006801:Humans; D007111:Immunity, Cellular; D012697:Serine Endopeptidases / Q000502:physiology*; D015398:Signal Transduction; D013602:T-Lymphocytes, Cytotoxic / Q000502:physiology*; D019014:fas Receptor / Q000502:physiology
D029742:Caenorhabditis elegans Proteins; D015853:Cysteine Proteinase Inhibitors; D019014:fas Receptor; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; C089223:ced-3 protein, C elegans