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International Immunology, Vol. 16, No. 2, pp. 241-247, February 2004
© 2004 Japanese Society for Immunology

Down-regulation of the invariant V{alpha}14 antigen receptor in NKT cells upon activation

Michishige Harada1, Ken-ichiro Seino1,2, Hiroshi Wakao1, Sakura Sakata1, Yuko Ishizuka1, Toshihiro Ito3, Satoshi Kojo1, Toshinori Nakayama3 and Masaru Taniguchi1

1 RIKEN Research Center for Allergy and Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan 2 PRESTO, JST, Kawaguchi City, Saitama 332-0012, Japan 3 Department of Medical Immunology, Graduate School of Medicine, Chiba University, Chiba City, Chiba 260-8670, Japan

Correspondence to: M. Taniguchi, RIKEN Research Center for Allergy and Immunology, Department of Molecular Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. E-mail: mtaniguchi{at}faculty.chiba-u.jp
Transmitting editor: T. Watanabe

NKT cells expressing the invariant V{alpha}14 antigen receptor constitute a novel lymphocyte subpopulation with immunoregulatory functions. Stimulation via their invariant V{alpha}14 receptor with anti-CD3 or a ligand, {alpha}-galactosylceramide ({alpha}-GalCer), triggers activation of V{alpha}14 NKT cells, resulting in a rapid cytokine production such as IFN-{gamma} and IL-4. Soon after their receptor activation, V{alpha}14 NKT cells disappeared as judged by staining with CD1d tetramer loaded with {alpha}-GalCer ({alpha}-GalCer/CD1d tetramer), which has been believed to be due to apoptotic cell death. Here we show that such a disappearance was largely attributed to down-regulation of the V{alpha}14 receptor. In fact, V{alpha}14 NKT cells were relatively resistant to apoptosis compared to the conventional T cells as evidenced by less staining with Annexin-V, a limited DNA fragmentation, and their preferential expression of anti-apoptotic genes such as NAIP and MyD118. Furthermore, they did not become tolerant, and maintained their proliferative capacity and cytokine production even after their receptor down-regulation. These as yet unrecognized facets of V{alpha}14 NKT cells are discussed in relation to their regulatory functions.

Keywords: {alpha}-galactosylceramide, apoptosis, CD1d tetramer, cDNA array, cytokine production


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