Abstract
TRAIL, the TNF-related apoptosis-inducing ligand, induces apoptosis of tumor cells, but not normal cells; the roles of TRAIL in nontransformed tissues are unknown. Using a soluble TRAIL receptor, we examined the consequences of TRAIL blockade in an animal model of multiple sclerosis. We found that chronic TRAIL blockade in mice exacerbated experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein. The exacerbation was evidenced primarily by increases in disease score and degree of inflammation in the CNS. Interestingly, the degree of apoptosis of inflammatory cells in the CNS was not affected by TRAIL blockade, suggesting that TRAIL may not regulate apoptosis of inflammatory cells in experimental autoimmune encephalomyelitis. By contrast, myelin oligodendrocyte glycoprotein-specific Th1 and Th2 cell responses were significantly enhanced in animals treated with the soluble TRAIL receptor. Based on these observations, we conclude that unlike TNF, which promotes autoimmune inflammation, TRAIL inhibits autoimmune encephalomyelitis and prevents activation of autoreactive T cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Animals
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Apoptosis / genetics
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Apoptosis / immunology*
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Apoptosis Regulatory Proteins
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Cells, Cultured
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Cytokines / biosynthesis
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Encephalomyelitis, Autoimmune, Experimental / etiology
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Encephalomyelitis, Autoimmune, Experimental / immunology*
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Encephalomyelitis, Autoimmune, Experimental / pathology*
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Female
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Humans
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Injections, Subcutaneous
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Jurkat Cells
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K562 Cells
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Ligands
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Membrane Glycoproteins / antagonists & inhibitors
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Membrane Glycoproteins / metabolism
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Membrane Glycoproteins / physiology*
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Mice
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Mice, Inbred C57BL
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Myelin Proteins
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Myelin-Associated Glycoprotein / immunology
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Myelin-Associated Glycoprotein / toxicity
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Myelin-Oligodendrocyte Glycoprotein
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Oligodendroglia / immunology
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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor / administration & dosage
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology
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Recombinant Proteins / administration & dosage
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Recombinant Proteins / biosynthesis
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Recombinant Proteins / pharmacology
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Solubility
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Spinal Cord / immunology
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Spinal Cord / pathology
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T-Lymphocytes / immunology
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T-Lymphocytes / metabolism
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T-Lymphocytes / pathology
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TNF-Related Apoptosis-Inducing Ligand
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Tumor Necrosis Factor-alpha / antagonists & inhibitors
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Tumor Necrosis Factor-alpha / metabolism
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Tumor Necrosis Factor-alpha / physiology*
Substances
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Apoptosis Regulatory Proteins
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Cytokines
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Ligands
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MOG protein, human
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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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Receptors, TNF-Related Apoptosis-Inducing Ligand
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Receptors, Tumor Necrosis Factor
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Recombinant Proteins
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TNF-Related Apoptosis-Inducing Ligand
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TNFRSF10B protein, human
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TNFSF10 protein, human
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Tnfrsf10b protein, mouse
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Tnfsf10 protein, mouse
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Tumor Necrosis Factor-alpha