ICOS costimulates invariant NKT cell activation.
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.
Kaneda
Hiroshi
H
Department of Immunology, Juntendo University School of Medicine, Tokyo 113-8421, Japan.
Takeda
Kazuyoshi
K
Ota
Tsuyoshi
T
Kaduka
Yuki
Y
Akiba
Hisaya
H
Ikarashi
Yoshinori
Y
Wakasugi
Hiro
H
Kronenberg
Mitchell
M
Kinoshita
Katsuyuki
K
Yagita
Hideo
H
Okumura
Ko
K
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*
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