Immune regulation of oral disease by co-signal molecule B7-H3 and the novel receptor.

• Project/Area Number: 21592385
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Pathobiological dentistry/Dental radiology
• Research Institution: Dokkyo Medical University (2010-2011); Tokyo Medical and Dental University (2009)
• Principal Investigator: HASHIGUCHI Masaaki 獨協医科大学, 医学部, 免疫学講座 (20372443)
• Co-Investigator(Kenkyū-buntansha): AZUMA Miyuki 東京医科歯科大学, 大学院・医歯学総合研究科, 教授 (90255654)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 免疫 / 感染 / 炎症 / ヒト免疫応答 / 補助シグナル / B7-H3 / TLT2 / 抗腫瘍免疫 / Tlt2

Research Abstract

Co-signal molecules play important roles in positively or negatively regulate cell responses. We previously reported that new cosignal ligand murine B7-H3 and the receptor TLT-2 enhance T cell responses. Here we investigate the precise mechanisms and found, in human system, B7-H3 upregulate T cell responses through the ligation with TLT-2, too. We also clarified TLT-2 upregulates anti-tumor immunity through the enhancement of cytotoxicity by CD8^+T cells. These suggest that B7-H3.TLT-2 enhances anti-tumor immunity and imply that strong or continuous B7-H3.TLT-2 signaling lowers TLT-2.

Research Products

• [Journal Article] Human B7-H3 binds to Triggering receptor expressed on myeloid cell-like transcript 2(TLT-2) and enhances T cell responses. Open J (2012)
  • Author(s): M. Hashiguchi, Y. Inamochi, S. Nagai, S., N. Otsuki, P. Jinhua, H. Kobori, Y. Kanno, T. Kobata, M. Azuma
  • Journal Title: Immunol. Peer-reviewed Volume: 2 Issue: 01 Pages: 9-16
  • DOI: 10.4236/oji.2012.21002
  • Peer Reviewed
• [Journal Article] Enhancement of effector CD8^+T cell function by tumor-associated B7-H3 and modulation of its counter receptor triggering receptor expressed on myeloid cell-like transcript 2(TLT-2) at tumor sites (2010)
  • Author(s): H. Kobori, M. Hashiguchi, J. Piao, M. Kato, P. Ritprajak, M. Azuma
  • Journal Title: Immunology Peer-reviewed Volume: 130 Issue: 3 Pages: 363-373
  • DOI: 10.1111/j.1365-2567.2009.03236.x
• [Journal Article] Enhancement of effector CD8^+ T cell function by tumor-associated B7-H3 and modulation of its counter receptor triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) at tumor sites (2010)
  • Author(s): H.Kobori, 他
  • Journal Title: Immunology Volume: 130 Pages: 363-373
  • Peer Reviewed
• [Journal Article] Enhancement of effector CD8^+ T cell function by tumor-associated B7-H3 and modulation of its counter receptor triggering receptor expressed on myeloid cell-like transcript 2 (TLT-2) at tumor sites (2010)
  • Author(s): H.Kobori, M.Hashiguchi, J.Piao, M.Kato, P.Ritprajak, M.Azuma
  • Journal Title: Immunology 130
  • Peer Reviewed
• [Presentation] Triggering receptor expressed on myeloid cells-like transcript 2 (TLT-2) is a counter-receptor for B7-H3 (2010)
  • Author(s): M.Hashiguchi
  • Organizer: The 14th International Congress of Immunology
  • Place of Presentation: 神戸
  • Year and Date: 2010-08-27
• [Presentation] Enhancement of effector CD8^+T cell function by tumor-associated B7-H3 and modulation of its counter receptor triggering receptor expressed on myeloid cell-like transcript 2(TLT-2) at tumor sites (2010)
  • Author(s): H. Kobori, M Hashiguchi, M. Azuma
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] Triggering receptor expressed on myeloid cells-like transcript 2(TLT-2) is a counter-receptor for B7-H3 and enhances T cell responses in mice and humans (2010)
  • Author(s): M. Hashiguchi, H. Kobori, P. Ritprajak, Y. Kamimura, M. Azuma
  • Organizer: 14th International Congress of Immunology
  • Place of Presentation: Kobe, Japan
  • Year and Date: 2010-08-26
• [Presentation] Binding property, expression, and function of human TLT2, a counter-receptor for B7-H3 (2009)
  • Author(s): M. Hashiguchi, H. Kobori, M. Azuma
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Tumor-infiltrating CD8^+T cells express TLT-2, a counter receptor for B7-H3 and B7-H3-transduced tumors preferentially augment effector function of CD8^+T cells (2009)
  • Author(s): H. Kobori, M. Hashiguchi, M. Azuma
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Tumor-infiltrating CD8+ T cells express TLT-2, a counter receptor for B7-H3 and B7-H3-transduced tumors preferentially augment effector function of CD8^+ T cells (2009)
  • Author(s): H.Kobori, M.Hashiguchi, M.Azuma.
  • Organizer: 日本免疫学会学術集会
  • Place of Presentation: 大阪
  • Year and Date: 2009-12-03
• [Presentation] Analyses of anti-tumor immunity enhanced by a B7-H3 costimulator (2009)
  • Author(s): H. Kobori, M. Hashiguchi, M. Azuma
  • Organizer: 日本癌学会学術集会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-02