ICOS costimulates invariant NKT cell activation

Hiroshi Kaneda; Kazuyoshi Takeda; Tsuyoshi Ota; Yuki Kaduka; Hisaya Akiba; Yoshinori Ikarashi; Hiro Wakasugi; Mitchell Kronenberg; Katsuyuki Kinoshita; Hideo Yagita; Ko Okumura

doi:10.1016/j.bbrc.2004.12.004

ICOS costimulates invariant NKT cell activation

Biochem Biophys Res Commun. 2005 Feb 4;327(1):201-7. doi: 10.1016/j.bbrc.2004.12.004.

Authors

Hiroshi Kaneda¹, Kazuyoshi Takeda, Tsuyoshi Ota, Yuki Kaduka, Hisaya Akiba, Yoshinori Ikarashi, Hiro Wakasugi, Mitchell Kronenberg, Katsuyuki Kinoshita, Hideo Yagita, Ko Okumura

Affiliation

¹ Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.

PMID: 15629449
DOI: 10.1016/j.bbrc.2004.12.004

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Animals
Antigens, CD1 / immunology
Antigens, CD1 / metabolism*
Antigens, CD1d
Antigens, Differentiation, T-Lymphocyte / genetics
Antigens, Differentiation, T-Lymphocyte / immunology
Antigens, Differentiation, T-Lymphocyte / metabolism*
CD28 Antigens / immunology
CD28 Antigens / metabolism
Cells, Cultured
Galactosylceramides / pharmacology
Inducible T-Cell Co-Stimulator Protein
Interferon-gamma / biosynthesis
Interferon-gamma / metabolism
Interleukin-4 / biosynthesis
Interleukin-4 / metabolism
Lymphocyte Activation / drug effects
Lymphocyte Activation / immunology*
Mice
Mice, Knockout
Signal Transduction
T-Lymphocyte Subsets / cytology
T-Lymphocyte Subsets / drug effects
T-Lymphocyte Subsets / immunology*
T-Lymphocyte Subsets / metabolism*

Substances

Antigens, CD1
Antigens, CD1d
Antigens, Differentiation, T-Lymphocyte
CD28 Antigens
Galactosylceramides
Icos protein, mouse
Inducible T-Cell Co-Stimulator Protein
alpha-galactosylceramide
Interleukin-4
Interferon-gamma