Abstract
Among the death ligands of the tumor necrosis factor/nerve growth factor (TNF/NGF) superfamily, TNF-related apoptosis-inducing ligand (TRAIL) is considered to play a unique role due to its binding to both apoptosis-inducing and -blocking membranous receptors, apoptosis-independent effects and distinct species differences. Here, we demonstrate that human antigen-specific T helper cells upon activation are capable of directly lysing glioma cell lines via TRAIL receptor/TRAIL interactions. Out of 17 T cell lines, nine showed predominantly TRAIL-mediated killing of glioma cell lines compared to CD95 ligand- or TNF-induced cell death. The cytotoxic potential of the T cell lines was independent of T helper differentiation, antigen specificity and donor source. Thus, TRAIL-mediated signaling is involved in T cell cytotoxicity towards glioma cell lines, which might play an important role in tumor regression.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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Brain Neoplasms*
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Cell Differentiation / immunology
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Epitopes
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Fas Ligand Protein
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Glioma*
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Humans
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / metabolism*
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / metabolism
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T-Lymphocytes, Cytotoxic / immunology*
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T-Lymphocytes, Helper-Inducer / immunology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Cells, Cultured
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism*
Substances
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Apoptosis Regulatory Proteins
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Epitopes
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FASLG protein, human
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Fas Ligand Protein
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Membrane Glycoproteins
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10A protein, human
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TNFSF10 protein, human
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Tumor Necrosis Factor-alpha