Challenges towards the generation of the dream immunosuppressant for the 21stcentury without permanent medication

• Project/Area Number: 23658093
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Applied biochemistry
• Research Institution: Hiroshima University
• Principal Investigator: KAWAMOTO Seiji 広島大学, 大学院・先端物質科学研究科, 准教授 (90294537)
• Project Period (FY): 2011 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 拒絶反応 / 制御性 T 細胞 / 免疫抑制抗体 / 制御性T細胞 / 国際情報交流

Research Abstract

Immunosuppressant is essential for transplantation, but current drug has problems such as the need of permanent medication or the risk of fatal side effects. In the present study, I sought to elucidate the mode of action of immunosuppressive antibody (anti-H1 antibody) induced in a rat model of tolerogeneic liver transplantation, and demonstrate its therapeutic efficacy in vivo. Here I found that the immunosuppressive anti-H1 antibody acted directly on T cells to exert its immunosuppressive activity, and that the anti-H1 antibody suppressed T cell activation in regulatory T cell dependent- and -independent mechanisms. I also showed that the anti-H1 antibody prolonged allograft survival in a rat model of heterotopic heart transplantation.

Research Products

• [Journal Article] Unexpected T cell regulatory activity of anti-histone H1 autoantibody: its mode of action in regulatory T cell-dependent and -independent manners. (2013)
  • Author(s): Takaoka Y., Kawamoto S., Katayama A., Nakano T., Yamanaka Y., Takahashi M., Shimada Y., Chiang K. C., Ohmori N., Aki T., Goto T., Sato S., Goto S., Chen C. L., Ono K.
  • Journal Title: Biochem. Biophys. Res. Commun Volume: 431 Pages: 246-252
  • Peer Reviewed
• [Journal Article] Unexpected T cell regulatory activity of anti-histone H1 autoantibody: its mode of action in regulatory T cell-dependent and -independent manners (2013)
  • Author(s): Yuki Takaoka
  • Journal Title: Biochemical and Biophysical Research Communications Volume: 431 Issue: 2 Pages: 246-252
  • DOI: 10.1016/j.bbrc.2012.12.125
  • Peer Reviewed
• [Journal Article] Immunological and regenerative aspects of hepatic mast cells in liver allograft rejection and tolerance (2012)
  • Author(s): Nakano T., Lai C. Y., Goto S., Hsu L. W., Kawamoto S., Ono K., Chen K. D., Lin C. C., Chiu K. W., Wang C. C., Cheng Y. F., Chen C. L.
  • Journal Title: PLoS ONE Volume: 7
  • NAID: 120005300479
  • Peer Reviewed
• [Journal Article] Autoimmunity and liver transplantation immunology (2011)
  • Author(s): Goto S., Nakano T., Hsu L. W., Chiang K. C., Lai C. Y., Kawamoto S., Ono K., Chen K. D., Ohmori N., Goto T., Sato S., Wang C. C., Jawan B., Cheng F. Y., Chen C. L.
  • Journal Title: Curr. Trends Immunol Volume: 12 Pages: 1-11
  • Peer Reviewed
• [Journal Article] Autoimmunity and liver transplantation immunology (2011)
  • Author(s): Shigeru Goto et al.
  • Journal Title: Current Trends in Immunology Volume: 12 Pages: 1-11
  • Peer Reviewed
• [Presentation] A unique T cell regulatory role of anti-histone H1 autoantibody: its mode of actionthrough regulatory T cell-dependent and -independent mechanisms. (2013)
  • Author(s): Takaoka Y., Kawamoto S., Katayama A., Nakano T., Takahashi M., Odawara S., Shimada Y., Chiang K. C., Ohmori N., Aki T., Goto T., Sato S., Goto S., Chen C. L., Ono K.
  • Organizer: The 13thFederation of Clinical Immunology Societies (FOCIS 2013)
  • Place of Presentation: Boston, Massachusetts, USA