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

The inducible costimulatory molecule (ICOS) is expressed on activated T cel ls and participates in a variety of important immunoregulatory functions. A fter the induction of experimental allergic encephalomyelitis in SJL mice w ith proteolipid protein (PLP), brain ICOS mRNA and protein were up-regulate d on infiltrating CD3(+) T cells before disease onset. ICOS blockade during the efferent immune response (9-20 days after immunization) abrogated dise ase, but blockade during antigen priming (1-10 days after immunization) exa cerbated disease. Upon culture with PLP and compared with immunized control s, splenocytes produced either decreased interferon-gamma (IFN-gamma, in ef ferent blockade) or excessive IFN-gamma (in priming blockade). PLP-specific immunoglobulin GI was decreased in animals treated with anti-ICOS during a ntigen priming, but not in other groups.