Basic studies for induction of tolerance by a cell-therapy

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670548
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Hokkaido University
• Principal Investigator: YAMASHITA KENICHIRO 北海道大学, 医学(系)研究科(研究院), 特任教授 (00399940)
• Co-Investigator(Kenkyū-buntansha): GOTO Ryoichi 北海道大学, 北海道大学病院, 医員 (10645287) ; AOYAGI Takeshi 北海道大学, 北海道大学病院, 医員 (90374347)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 移植免疫 / 免疫抑制性 / 細胞治療 / 分子標的

Outline of Final Research Achievements

In this study, we performed basic researches on immunoregulatory cells in order to search for new immunosuppressive strategies. We found that tolerogeneic dendritic cells (tDCs) were successfully generated ex-vivo by suppressing activation of either NF-κB or MAPKs in the presence of donor-peptide antigens, and that administration of these tDCs significantly prolonged allograft survival in mice. The inhibition of NF-κB, MAPKs or AP-1/mTOR/p70S6K activation following infusion of donor-leukocytes exerted a potent immunosuppressive effect. In some of these protocols, regulatory T cells (Tregs) were effectively induced in vivo. Coculture of peripheral blood mononuclear cells and allo-antigens together with either CD80/86- or CD40-costimulation blockers induced antigen-specific Tregs that seemed to have a potential utility for clinical immunosuppression.

Free Research Field

臓器移植