title: ICOS costimulates invariant NKT cell activation.
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.
authors.affiliation: Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kaneda
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Takeda
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ota
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kaduka
authors.forename: Hisaya
authors.initials: H
authors.lastname: Akiba
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Ikarashi
authors.forename: Hiro
authors.initials: H
authors.lastname: Wakasugi
authors.forename: Mitchell
authors.initials: M
authors.lastname: Kronenberg
authors.forename: Katsuyuki
authors.initials: K
authors.lastname: Kinoshita
authors.forename: Hideo
authors.initials: H
authors.lastname: Yagita
authors.forename: Ko
authors.initials: K
authors.lastname: Okumura
mesh_terms: D000818:Animals; D018949:Antigens, CD1 / Q000276:immunology / Q000378:metabolism*; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D018106:CD28 Antigens / Q000276:immunology / Q000378:metabolism; D002478:Cells, Cultured; D005699:Galactosylceramides / Q000494:pharmacology; D060889:Inducible T-Cell Co-Stimulator Protein; D007371:Interferon-gamma / Q000096:biosynthesis / Q000378:metabolism; D015847:Interleukin-4 / Q000096:biosynthesis / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D018949:Antigens, CD1; D055610:Antigens, CD1d; D000945:Antigens, Differentiation, T-Lymphocyte; D018106:CD28 Antigens; D005699:Galactosylceramides; C556694:Icos protein, mouse; D060889:Inducible T-Cell Co-Stimulator Protein; C493154:alpha-galactosylceramide; D015847:Interleukin-4; D007371:Interferon-gamma