Abstract
TNF-related apoptosis-inducing ligand (TRAIL), a new member of TNF family, induces apoptotic cell death of various tumor cells. We recently showed that TRAIL mediates perforin- and Fas ligand (FasL)-independent cytotoxic activity of human CD4+ T cell clones. In the present study, we investigated the expression and function of TRAIL on murine lymphocytes by using newly generated anti-murine TRAIL mAbs. Although freshly isolated T, B, or NK cells did not express a detectable level of TRAIL on their surface, a remarkable level of TRAIL expression was induced preferentially on CD3- NK1.1+ NK cells after stimulation with IL-2 or IL-15. In contrast, TRAIL expression was not induced by IL-18, whereas it efficiently potentiated lymphokine-activated killer activity of NK cells. In addition to perforin inactivation and neutralization of FasL by anti-FasL mAb, neutralization of TRAIL by anti-TRAIL mAb was needed for the complete inhibition of IL-2- or IL-15-activated NK cell cytotoxicity against mouse fibrosarcoma L929 target cells, which were susceptible to both FasL and TRAIL. These results indicated preferential expression of TRAIL on IL-2- or IL-15-activated NK cells and its potential involvement in lymphokine-activated killer activity.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antibodies, Monoclonal / chemistry
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Antibodies, Monoclonal / metabolism
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Apoptosis / genetics
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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Cell Line
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Cytotoxicity, Immunologic
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Humans
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Interleukin-15 / pharmacology
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Interleukin-2 / pharmacology
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Killer Cells, Natural / immunology*
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Killer Cells, Natural / metabolism*
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Ligands
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Lymphocyte Activation* / genetics
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Male
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / immunology
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Membrane Glycoproteins / metabolism
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Mice
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Mice, Inbred C57BL
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Rats
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Rats, Inbred F344
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / chemistry
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Recombinant Proteins / immunology
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Recombinant Proteins / metabolism
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TNF-Related Apoptosis-Inducing Ligand
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Transfection
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics
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Tumor Necrosis Factor-alpha / immunology
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Tumor Necrosis Factor-alpha / metabolism
Substances
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Antibodies, Monoclonal
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Apoptosis Regulatory Proteins
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Interleukin-15
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Interleukin-2
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Ligands
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Membrane Glycoproteins
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Recombinant Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFSF10 protein, human
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Tnfsf10 protein, mouse
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Tnfsf10 protein, rat
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Tumor Necrosis Factor-alpha