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Publication : ICOS costimulates invariant NKT cell activation.

First Author  Kaneda H Year  2005
Journal  Biochem Biophys Res Commun Volume  327
Issue  1 Pages  201-7
PubMed ID  15629449 Mgi Jnum  J:95353
Mgi Id  MGI:3525897 Doi  10.1016/j.bbrc.2004.12.004
Citation  Kaneda H, et al. (2005) ICOS costimulates invariant NKT cell activation. Biochem Biophys Res Commun 327(1):201-7
abstractText  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.
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