Abstract
Apo-2L is a new member of the tumour necrosis factor (TNF) family shown to induce apoptosis in a number of tumour cell lines. Apo-2L mRNA is expressed by numerous human tissues. Here we report that Apo-2L is expressed and utilized by human Natural Killer (NK) cells. NK cells were shown to express surface Apo-2L in response to interleukin 2 (IL-2) activation, and this response was restricted to the CD3(-)population of the NK cells. Apo-2L mRNA and intracellular Apo-2L were present in both CD3(-)and CD3(+)NK cells; however, increased expression in response to IL-2 was only observed in CD3(-)CD56(+)cells. Also, IL-2-activated NK cells were shown to utilize membrane-bound Apo-2L in mediating lysis of Jurkat cells. Furthermore, Apo-2L-induced apoptosis of Jurkat cells was more rapid than FasL-induced apoptosis, indicating an important and distinct role for Apo-2L in apoptotic cell destruction. In conclusion, we report that NK cells express Apo-2L and that IL-2 activated CD3(-)NK cells utilize the Apo-2L pathway in mediating target cell lysis.
Copyright 1999 Academic Press.
Publication types
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Antibodies, Monoclonal / pharmacology
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Apoptosis / drug effects*
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Apoptosis / genetics
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Apoptosis / physiology
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Apoptosis Regulatory Proteins
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Cytotoxicity, Immunologic*
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Fas Ligand Protein
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Gene Expression Regulation* / drug effects
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Humans
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Immunophenotyping
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Interleukin-2 / pharmacology
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Jurkat Cells / drug effects
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Jurkat Cells / pathology
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Killer Cells, Natural / drug effects
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Killer Cells, Natural / immunology
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Killer Cells, Natural / metabolism*
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Membrane Glycoproteins / biosynthesis*
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Membrane Glycoproteins / genetics
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Membrane Glycoproteins / pharmacology
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RNA, Messenger / biosynthesis
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Recombinant Proteins / pharmacology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / biosynthesis*
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Tumor Necrosis Factor-alpha / genetics
Substances
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Antibodies, Monoclonal
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Apoptosis Regulatory Proteins
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FASLG protein, human
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Fas Ligand Protein
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Interleukin-2
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Membrane Glycoproteins
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RNA, Messenger
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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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Tumor Necrosis Factor-alpha