| Literature DB >> 15629449 |
Hiroshi Kaneda1, Kazuyoshi Takeda, Tsuyoshi Ota, Yuki Kaduka, Hisaya Akiba, Yoshinori Ikarashi, Hiro Wakasugi, Mitchell Kronenberg, Katsuyuki Kinoshita, Hideo Yagita, Ko Okumura.
Abstract
It has been reported that costimulatory molecules, CD80/86-CD28 and CD154-CD40, critically contribute to activation of CD1d-restricted invariant NKT (iNKT) cells. Here we have demonstrated that ICOS, a new member of the CD28 family, plays a substantial role in iNKT cell activation. iNKT cells constitutively expressed ICOS as well as CD28 independently, and ICOS expression was further up-regulated 2-3 days after alpha-galactosylceramide (alpha-GalCer) treatment. Blockade of ICOS-mediated costimulation by administration of anti-ICOS ligand (B7RP-1) mAb or by ICOS gene knockout substantially inhibited alpha-GalCer-induced IFN-gamma and IL-4 production, cytotoxic activity, and anti-metastatic effect. Moreover, blockade of both B7RP-1-ICOS and CD80/86-CD28 interactions mostly abolished the alpha-GalCer-induced immune responses. These findings indicate that iNKT cell activation is regulated by CD28 and IOCS independently.Entities:
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Year: 2005 PMID： 15629449 DOI： 10.1016/j.bbrc.2004.12.004
Source DB: PubMed Journal: Biochem Biophys Res Commun ISSN： 0006-291X Impact factor: 3.575