2008 Fiscal Year Final Research Report
Induction of autoimmune diseases through activation of B-1 cells by Helicobacter pylori urease
| Project/Area Number |
18590705
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Gastroenterology
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| Research Institution | Nippon Medical School |
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Principal Investigator |
TAKAHASHI Hidemi Nippon Medical School, 大学院・医学研究科, 教授 (40221361)
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| Project Period (FY) |
2006 – 2008
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| Keywords | Helicobacter pylori / urease / B-1細胞 / 自己抗体 / 自己免疫疾患 / リウマチ因子 |
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| Research Abstract |
報告者らは、ピロリ菌より採取・精製した菌体制分ウレアーゼが、ヘルパーT細胞の非存在下でマウス由来のB-1細胞を選択的に活性化すること、そしてこうしたB-1細胞をピロリ菌ウレアーゼで刺激したところ、培養上清中に自己抗体としてのリウマチ因子(RF)や抗DNA抗体が放出されることを発見した。また、ピロリ菌の培養上清中には全く菌体由来ウレアーゼ蛋白は検出されないこと、ならびに菌体表面に多量のウレアーゼ蛋白が発現していることを確認した。そこで、ウレアーゼを欠損したピロリ菌を入手し、このウレアーゼ欠損株と非欠損株ピロリ菌をプレート上に固着させ、B-1細胞を添加培養し、上清中のリウマチ因子や抗DNA抗体の放出量を測定したところ、ウレアーゼ非欠損株とともに培養した場合においてのみ、これらの自己抗体が検出された。こうした事実は、ピロリ菌表面のLPSなどではなく、菌体表面に発現したウレアーゼが直接にB-1細胞を刺激し、自己抗体の産生・放出を促したことを示している(論文投稿中)。
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[Journal Article] Functional B7.2 and B7-H2 molecules on myeloma cells are associated with a growth advantage2009
Author(s)
Yamashita, T., Tamura, H., Satoh, C., Shinya, E., Takahashi, H., Chen, L., Kondo, A., Tsuji, T., Dan, K., Ogata, K.
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Journal Title
Clin. Cancer Res 75
Pages: 152-158
Peer Reviewed
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[Journal Article] Small intestine CD4+ T cells are profoundly depleted during acute simian-human immunodeficiency virus infection, regardless of viral pathogenicity2008
Author(s)
Fukazawa, Y., Miyake, A., Ibuki, K., Inaba, K., Saito, N., Motohara, M., Horiuchi, R., Himeno, A., Matsuda, K., Matsuyama, M., Takahashi, H., Hayami, M., Igarashi, T., Miura, T.
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Journal Title
J. Virol 82
Pages: 6039-6044
Peer Reviewed
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[Journal Article] Importance of gastrointestinal ingestion and macromolecular antigens in the vein for oral tolerance induction2007
Author(s)
Wakabayashi, A., Kumagai, Y., Watari, E., Shimizu, M., Utsuyama, M., Hirokawa, K., Takahashi, H.
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Journal Title
Immunology 119
Pages: 167-177
Peer Reviewed
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[Journal Article] A possible mechanism of intravesical BCG therapy for human bladder carcinoma : involvement of innate effector cells for the inhibition of tumor growth2007
Author(s)
Higuchi, T., Shimizu, M., Owaki, A., Takahashi, M., Shinya, E., Nishimura, T., Takahashi, H.
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Journal Title
Cancer Immunol. Immunother. Jan 13, online published
Peer Reviewed
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[Journal Article] Implications for induction of autoimmunity via activation of B-1 cells by Helicobacter pylori urease2006
Author(s)
Yamanishi, S., Iizumi, T., Watanabe, E., Shimizu, M., Kamiya, S., Nagata, K., Kumagai, Y., Fukunaga, Y., Takahashi, H.
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Journal Title
Infect. Immune 74
Pages: 248-256
Peer Reviewed
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[Journal Article] Induction of immunological tolerance by oral, but not intravenous and intraportal, administration of ovalbumin and the difference between young and old mice2006
Author(s)
Wakabayashi A., Utsuyama, M., Hosoda, T., Sato., Takahashi, H., Hirokawa, K.
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Journal Title
J. Nutr. Health Aging 10
Pages: 183-191
Peer Reviewed
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[Journal Article] BCG vaccine elicits both T-cell mediated and humoral immune responses directed against mycobacterial lipid components2006
Author(s)
Watanabe Y, Watari E, Matsunaga I, Hiromatsu K, Dascher C D, Kawashima T, Norose Y, Simizu K, Takahashi H, Yano I, Sugita M
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Journal Title
Vaccine 24
Pages: 5700-5707
Peer Reviewed
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