Abstract
The inducible costimulatory molecule (ICOS) is expressed on activated T cells and participates in a variety of important immunoregulatory functions. After the induction of experimental allergic encephalomyelitis in SJL mice with proteolipid protein (PLP), brain ICOS mRNA and protein were up-regulated on infiltrating CD3+ T cells before disease onset. ICOS blockade during the efferent immune response (9-20 days after immunization) abrogated disease, but blockade during antigen priming (1-10 days after immunization) exacerbated disease. Upon culture with PLP and compared with immunized controls, splenocytes produced either decreased interferon-gamma (IFN-gamma, in efferent blockade) or excessive IFN-gamma (in priming blockade). PLP-specific immunoglobulin G1 was decreased in animals treated with anti-ICOS during antigen priming, but not in other groups.
MeSH terms
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Animals
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Antigens, Differentiation, T-Lymphocyte / genetics
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Antigens, Differentiation, T-Lymphocyte / immunology*
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B7-1 Antigen / genetics
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B7-1 Antigen / immunology
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Brain / immunology
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Brain / pathology
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Cytokines / biosynthesis
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Cytokines / genetics
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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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Immunoglobulin G / biosynthesis
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Inducible T-Cell Co-Stimulator Ligand
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Inducible T-Cell Co-Stimulator Protein
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Interferon-gamma / biosynthesis
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Mice
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Myelin Proteolipid Protein / adverse effects
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Myelin Proteolipid Protein / immunology
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T-Lymphocytes / immunology
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Up-Regulation / immunology
Substances
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Antigens, Differentiation, T-Lymphocyte
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B7-1 Antigen
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Cytokines
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Icos protein, mouse
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Immunoglobulin G
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Inducible T-Cell Co-Stimulator Ligand
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Inducible T-Cell Co-Stimulator Protein
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Myelin Proteolipid Protein
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Interferon-gamma