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International Immunology Advance Access originally published online on May 9, 2008
International Immunology 2008 20(7):849-860; doi:10.1093/intimm/dxn043
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© The Japanese Society for Immunology. 2008. All rights reserved. For permissions, please e-mail: journals.permissions@oxfordjournals.org

Human Th1 differentiation induced by lipoarabinomannan/lipomannan from Mycobacterium bovis BCG Tokyo-172

Toshihiro Ito1, Akihiro Hasegawa1, Hiroyuki Hosokawa1, Masakatsu Yamashita1, Shinichiro Motohashi1, Takashi Naka2, Yuko Okamoto2, Yukiko Fujita2, Yasuyuki Ishii3, Masaru Taniguchi3, Ikuya Yano2 and Toshinori Nakayama1

1 Department of Immunology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan
2 Japan BCG Laboratory, 3-1-5 Matsuyama, Kiyose, Tokyo 204-0022, Japan
3 RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan

1 Correspondence to: T. Nakayama; E-mail: tnakayama{at}faculty.chiba-u.jp

Mycobacterium tuberculosis (tubercle bacilli) and the related acid-fast bacteria including Mycobacterium bovis Bacille Calmett–Guerin (BCG) have a characteristic cell wall (CW) containing various lipoglycans and glycolipids. Such lipoglycans have been reported to activate type-I inflammatory responses via dendritic cells (DCs) through Toll-like receptor 2. In this study, lipoglycans, lipoarabinomannan (LAM), lipomannan (LM) and phosphatidylinositol mannoside (PIM), were purified from the CW fractions of M. bovis BCG Tokyo-172, and the effect on the differentiation of human peripheral blood naive CD4 T cells into Th1 and Th2 was examined. LAM/LM molecules enhanced Th1 differentiation under both Th1 and Th2 conditions, whereas some other glycolipids and phospholipid enhanced Th2 differentiation under Th2 conditions. Other components had little effect under the given conditions. Even in highly purified CD4 T cell cultures, LAM/LM enhanced Th1 generation only under Th1 culture conditions. These results indicate that LAM/LM possesses a potent augmenting activity in Th1 differentiation in human CD4 T cells. LAM/LM appeared to act directly on naive CD4 T cells to enhance Th1 differentiation under Th1 culture conditions, while acting indirectly to up-regulate the generation of Th1 cells via IL-12/DCs under Th1 and Th2 conditions. Therefore, these results provide the first evidence indicating that LAM/LM from M. bovis BCG may possess a potent modulating activity in the human system, and thus supporting the strategy for the use of BCG components in the vaccine development for such Th2 diseases as allergic asthma and rhinitis.

Keywords: DC, Th1/Th2, vaccination

Transmitting editor: A. Singer

Received 8 November 2007, accepted 8 April 2008.


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