Abstract
T-cell apoptosis in inflammatory demyelinating lesions of chronic myelin oligodendrocyte glycoprotein peptide35-55 induced autoimmune encephalomyelitis was studied in several different gene knockout mice as well as their wild-type counterparts. The gene deletions included tumor necrosis factor (TNF) alpha, lymphotoxin, TNF receptor 1 or 2, Fas-L, inducible nitric oxide synthase, perforin, and interleukin1beta-converting enzyme. Impairment of the TNF receptor 1 pathway led to a 50% reduction of T-cell apoptosis in the central nervous system lesions, whereas the other genetic deletions showed no significant effect. Our study thus identified the TNF receptor 1 signaling pathway as one mechanism responsible for the removal of T lymphocytes from inflammatory demyelinating lesions of the central nervous system.
MeSH terms
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Animals
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Apoptosis / physiology*
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Caspase 10
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Caspases / metabolism
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / physiopathology*
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Fas Ligand Protein
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Membrane Glycoproteins / physiology
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Mice
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Mice, Knockout
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Myelin Proteins
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Myelin-Associated Glycoprotein / chemistry
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Myelin-Associated Glycoprotein / toxicity*
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Myelin-Oligodendrocyte Glycoprotein
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Nitric Oxide Synthase / metabolism
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Nitric Oxide Synthase Type II
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Peptide Fragments / toxicity*
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Perforin
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Pore Forming Cytotoxic Proteins
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Receptors, Tumor Necrosis Factor / physiology*
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Signal Transduction / physiology*
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T-Lymphocytes / pathology*
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fas Receptor
Substances
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Fas Ligand Protein
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Fasl protein, mouse
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Membrane Glycoproteins
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Mog protein, mouse
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Myelin Proteins
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Myelin-Associated Glycoprotein
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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Pore Forming Cytotoxic Proteins
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Receptors, Tumor Necrosis Factor
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fas Receptor
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Perforin
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Nitric Oxide Synthase
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Nitric Oxide Synthase Type II
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Nos2 protein, mouse
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Caspase 10
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Caspases
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interleukin 1beta-converting enzyme 2