Abstract
Experimental autoimmune encephalomyelitis (EAE) is an inflammatory demyelinating disease with similarities to multiple sclerosis (MS). It is induced in mice by the transfer of myelin-reactive T cells. Here we demonstrate that IL-12 stimulates myelin-reactive T cells to up-regulate the beta-chemokine receptor, CCR5, in correlation with the acquisition of central nervous system-infiltrating and encephalitogenic properties. These effects of IL-12 are IFN gamma-independent. The CCR5 ligands, RANTES and MIP-1 alpha, are expressed in the spinal cords of mice at EAE onset. Our results suggest that reagents that block CCR5/beta-chemokine interactions and/or antagonize IL-12 might be useful for treatment of autoimmune demyelination.
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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Encephalomyelitis, Autoimmune, Experimental / immunology
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Encephalomyelitis, Autoimmune, Experimental / metabolism*
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Female
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Interferon-gamma / deficiency
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Interferon-gamma / genetics
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Interferon-gamma / physiology*
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Interleukin-12 / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Myelin Sheath / drug effects
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Myelin Sheath / immunology*
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Myelin Sheath / metabolism
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RNA, Messenger / biosynthesis
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Receptors, CCR5 / biosynthesis*
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T-Lymphocytes / drug effects
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T-Lymphocytes / immunology*
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T-Lymphocytes / metabolism
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Up-Regulation / drug effects
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Up-Regulation / immunology
Substances
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RNA, Messenger
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Receptors, CCR5
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Interleukin-12
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Interferon-gamma