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      The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE.

      Nature immunology

      Animals, Antigens, CD80, genetics, immunology, Antigens, Differentiation, T-Lymphocyte, Brain, pathology, Cytokines, biosynthesis, Encephalomyelitis, Autoimmune, Experimental, Female, Immunoglobulin G, Inducible T-Cell Co-Stimulator Ligand, Inducible T-Cell Co-Stimulator Protein, Interferon-gamma, Mice, Myelin Proteolipid Protein, adverse effects, T-Lymphocytes, Up-Regulation

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          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.

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          Journal
          11429544
          10.1038/89750

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