Abstract
The cytokine IL-21 is closely related to IL-2 and IL-15, a cytokine family that uses the common gamma-chain for signaling. IL-21 is expressed by activated CD4(+) T cells. We examined the role of IL-21 in the autoimmune disease experimental autoimmune encephalomyelitis (EAE), an animal model for human multiple sclerosis. IL-21 administration before induction of EAE with a neuroantigen, myelin oligodendrocyte glycoprotein peptide 35-55, and adjuvant enhanced the inflammatory influx into the CNS, as well as the severity of EAE. Autoreactive T cells purified from IL-21-treated mice transferred more severe EAE than did the control encephalitogenic T cells. No such effects were observed when IL-21 was administered after EAE progressed. Additional studies demonstrated that IL-21 given before the induction of EAE boosted NK cell function, including secretion of IFN-gamma. Depletion of NK cells abrogated the effect of IL-21. Therefore, IL-21, by affecting NK cells, has differential effects during the initiation and progression of autoimmune responses against neuroantigens.
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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Amino Acid Sequence
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Animals
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Autoantibodies / biosynthesis*
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B-Lymphocyte Subsets / immunology
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Cells, Cultured
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Disease Progression
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Dose-Response Relationship, Immunologic
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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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Glycoproteins / administration & dosage
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Glycoproteins / immunology*
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Immunization Schedule
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Interferon-gamma / biosynthesis
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Interleukin-21
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Interleukins / administration & dosage*
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Interleukins / antagonists & inhibitors
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Interleukins / physiology*
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Killer Cells, Natural / immunology
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Lymphocyte Depletion
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Molecular Sequence Data
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments / administration & dosage
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Peptide Fragments / immunology*
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T-Lymphocyte Subsets / immunology
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T-Lymphocyte Subsets / pathology
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Th1 Cells / immunology
Substances
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Autoantibodies
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Glycoproteins
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Interleukins
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Myelin-Oligodendrocyte Glycoprotein
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Peptide Fragments
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myelin oligodendrocyte glycoprotein (35-55)
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Interferon-gamma
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Interleukin-21