Nature Immunology
2, 605 - 611 (2001)
doi:10.1038/89750
The costimulatory molecule ICOS plays an important role in the immunopathogenesis of EAEJames B. Rottman, Tammy Smith, James R. Tonra, Kenneth Ganley, Troy Bloom, Robert Silva, Barbara Pierce, Jose-Carlos Gutierrez-Ramos, Engin Özkaynak
& Anthony J. Coyle
Millennium Pharmaceuticals, 640 Memorial Drive, Cambridge, MA 02139, USA.
Correspondence should be addressed to James B. Rottman jrottman@mpi.comThe 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- (IFN-, in efferent blockade) or excessive IFN- (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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