1. The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAE.
- Author
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Rottman JB, Smith T, Tonra JR, Ganley K, Bloom T, Silva R, Pierce B, Gutierrez-Ramos JC, Ozkaynak E, and Coyle AJ
- Subjects
- Animals, Antigens, Differentiation, T-Lymphocyte genetics, B7-1 Antigen genetics, B7-1 Antigen immunology, Brain immunology, Brain pathology, Cytokines biosynthesis, Cytokines genetics, Encephalomyelitis, Autoimmune, Experimental pathology, Female, Immunoglobulin G biosynthesis, Inducible T-Cell Co-Stimulator Ligand, Inducible T-Cell Co-Stimulator Protein, Interferon-gamma biosynthesis, Mice, Myelin Proteolipid Protein adverse effects, Myelin Proteolipid Protein immunology, T-Lymphocytes immunology, Up-Regulation immunology, Antigens, Differentiation, T-Lymphocyte immunology, Encephalomyelitis, Autoimmune, Experimental immunology
- 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.
- Published
- 2001
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