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Title: Invariant NKT cell anergy is induced by a strong TCR-mediated signal plus co-stimulation.
Authors: Iyoda, Tomonori
Ushida, Maki
Kimura, Yukino
Minamino, Kento
Hayuka, Akiko
Yokohata, Shoichi
Ehara, Hiromi
Inaba, Kayo  kyouindb  KAKEN_id
Author's alias: 稲葉, カヨ
Keywords: CD28
co-stimulation
dendritic cell
α-GalCer
in vivo
ionomycin
NKT cells
Issue Date: Nov-2010
Publisher: Oxford University Press
Journal title: International immunology
Volume: 22
Issue: 11
Start page: 905
End page: 913
Abstract: Vα14 TCR expressing invariant NK T (iNKT) cells recognize α-galactosylceramide (αGC)/CD1d complex and produce large amounts of various cytokines before the onset of the adaptive immunity. After stimulation with a high dose (2-5 μg) of αGC in vivo, iNKT cells in the spleen and liver become anergic in terms of the proliferation and cytokine production to subsequent stimulation. In this study, we monitor how iNKT anergy is induced. Anergized iNKT cells dramatically reduced the expression of IL-2Rα, and exogenous IL-2 restored the ability to proliferate and produce IL-4 but not to produce IFN-γ. Anergized iNKT cells expressed high levels of programmed death-1 (PD-1). However, iNKT cells in PD-1-deficient mice became anergic as a result of αGC injection, as do normal mice. Furthermore, anti-PD-1 blocking mAb was unable to restore their responsiveness. When iNKT cells were stimulated with immobilized anti-CD3 in the presence or absence of anti-CD28, they produced cytokines in a dose-dependent manner. Unlike in naive CD4 T cells, the strong TCR-mediated signaling with co-stimulation renders them anergic to any subsequent stimulation with αGC and spleen dendritic cells (DCs). Moreover, iNKT cells also became anergic after stimulation with phorbol-12-myristate-13-acetate + ionophore. Finally, the injection of αGC-pulsed DCs was more potent in inducing anergy than B cells. These results indicate that strong TCR-mediated activation with co-stimulation provides signals that induce the anergic state in iNKT cells.
Rights: © The Japanese Society for Immunology. 2010.
This is not the published version. Please cite only the published version. この論文は出版社版でありません。引用の際には出版社版をご確認ご利用ください。
URI: http://hdl.handle.net/2433/156274
DOI(Published Version): 10.1093/intimm/dxq444
PubMed ID: 21118907
Appears in Collections:Journal Articles

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