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

Nat Immunol. 2001 Jul;2(7):605-11. doi: 10.1038/89750.


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

  • Animals
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / immunology*
  • B7-1 Antigen / genetics
  • B7-1 Antigen / immunology
  • Brain / immunology
  • Brain / pathology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • 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
  • B7-1 Antigen
  • Cytokines
  • Icos protein, mouse
  • Immunoglobulin G
  • Inducible T-Cell Co-Stimulator Ligand
  • Inducible T-Cell Co-Stimulator Protein
  • Myelin Proteolipid Protein
  • Interferon-gamma