Abstract
We previously identified the NK cell receptor KIR3DL2 as a valuable diagnostic and prognostic marker for the detection of the tumoral T cell burden of Sézary syndrome (SS) patients. However, the function of this receptor on the malignant T lymphocyte population remained unexplored. We here demonstrate that engagement of KIR3DL2 by its recently identified ligand CpG oligodeoxynucleotide (ODN) induces the internalization of the receptor and leads to a caspase-dependent apoptosis of malignant T cells. This process of cellular death is correlated to a dephosphorylation of the transcription factor STAT3 (signal transducer and activator of transcription 3), which is found constitutively phosphorylated and activated in Sézary cells. Our results indicate that KIR3DL2 can directly promote SS malignant cell death through the use of CpG ODN.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Apoptosis / drug effects
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Apoptosis / immunology
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CD4-Positive T-Lymphocytes / drug effects
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CD4-Positive T-Lymphocytes / immunology
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CD4-Positive T-Lymphocytes / metabolism
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Cells, Cultured
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Humans
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Ligands
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Mycosis Fungoides / immunology*
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Mycosis Fungoides / metabolism
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Oligodeoxyribonucleotides / immunology*
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Oligodeoxyribonucleotides / metabolism
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Oligodeoxyribonucleotides / pharmacology
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Phosphorylation / drug effects
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Phosphorylation / immunology
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Receptors, KIR3DL2 / immunology*
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Receptors, KIR3DL2 / metabolism
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STAT3 Transcription Factor / immunology
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STAT3 Transcription Factor / metabolism
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Sezary Syndrome / immunology*
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Sezary Syndrome / metabolism
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Signal Transduction / drug effects
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Signal Transduction / immunology
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Skin Neoplasms / immunology*
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Skin Neoplasms / metabolism
Substances
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CPG-oligonucleotide
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KIR3DL2 protein, human
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Ligands
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Oligodeoxyribonucleotides
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Receptors, KIR3DL2
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STAT3 Transcription Factor
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STAT3 protein, human