Skip Navigation


International Immunology Advance Access originally published online on May 16, 2008
International Immunology 2008 20(7):869-879; doi:10.1093/intimm/dxn046
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow All Versions of this Article:
20/7/869    most recent
dxn046v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Ito, H.
Right arrow Articles by Seishima, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ito, H.
Right arrow Articles by Seishima, M.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?


© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Role of V{alpha}14+ NKT cells in the development of Hepatitis B virus-specific CTL: activation of V{alpha}14+ NKT cells promotes the breakage of CTL tolerance

Hiroyasu Ito1,2,*, Kazuki Ando1,3,*, Tetsuya Ishikawa4, Toshinori Nakayama5, Masaru Taniguchi6, Kuniaki Saito1,7, Michio Imawari8, Hisataka Moriwaki9, Takashi Yokochi2, Shinichi Kakumu10 and Mitsuru Seishima1

1 Department of Informative Clinical Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
2 Department of Microbiology and Immunology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan
3 Goto Clinic, Gifu 503-0899, Japan
4 Cancer Immunotherapy Center, Nagoya Kyoritsu Hospital, 1-172 Hokke, Nakagawa, Nagoya 454-0933, Japan
5 Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
6 RIKEN Research Center for Allergy and Immunology, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama City, Kanagawa 230-0045, Japan
7 Human Health Sciences, Graduate School of Medicine and Faculty of Medicine, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo, Kyoto 606-8507, Japan
8 Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan
9 First Department of Internal Medicine, Gifu University Graduate School of Medicine, 1-1 Yanagido, Gifu 501-1194, Japan
10 Division of Gastroenterology, Department of Internal Medicine, Aichi Medical University, Nagakute, Aichi 480-1195, Japan

Correspondence to: H. Ito; E-mail: hito{at}gifu-u.ac.jp

CTLs are thought to be major effectors for clearing viruses in acute infections including hepatitis B virus (HBV). Persistent HBV infection is characterized by a lack of or a weak CTL response to HBV, which is thought to reflect tolerance to HBV antigens. In the present study, we found that alpha-galactosylceramide ({alpha}-GalCer), a ligand for V{alpha}14-positive NKT cells, strongly enhanced the induction and proliferation of HBV-specific CTLs by HBsAg. In HBsAg transgenic mice, which are thought to be tolerant to HBV-encoded antigens, administration of HBsAg or {alpha}-GalCer alone failed to induce HBsAg-specific CTLs, but they were induced by co-administration of both compounds. Furthermore, by limiting dilution analysis, we confirmed the existence of HBsAg-specific CTL precursors in the HBsAg transgenic mice immunized with HBsAg and {alpha}-GalCer. A blocking experiment using antibodies to cytokines and CD40 ligand showed that IL-2 and CD40–CD40L interaction mediate the enhancement of CTL induction caused by {alpha}-GalCer through NKT cell activation. Our results may open up a new method for clearing the virus from patients with persistent HBV infection.

Keywords: CTL, hepatitis B virus, NKT cell

* These authors contributed equally to this study.

Transmitting editor: H. Karasuyama

Received 10 August 2007, accepted 16 April 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.