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Rottman, James B; Smith, Tammy; Tonra, James R; Ganley, Kenneth; Bloom, Troy; Silva, Robert; Pierce, Barbara; Gutierrez-Ramos, Jose-Carlos; Özkaynak, Engin; Coyle, Anthony J
Nature immunology, 07/2001, Letnik: 2, Številka: 7Journal Article
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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