Immunotolerance induction in kidney transplantation by infusion of regulatory cells

• Project/Area Number: 25461964
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Tokyo Women's Medical University
• Principal Investigator: Koyama Ichiro 東京女子医科大学, 医学部, 助教 (10266760)
• Co-Investigator(Kenkyū-buntansha): FUCHINOUE Shohei 東京女子医科大学, 医学部, 准教授 (10147382) ; TERAOKA Satoshi 国際医療福祉大学, 大学病院, 教授 (20147383) ; BASHUDA Hisashi 順天堂大学, 医学部, 助教 (40439295) ; OKUMURA Ko 順天堂大学, 医学部, 教授 (50009700) ; MURAKAMI Toru 東京女子医科大学, 医学部, 助教 (50287356) ; NAKAJIMA Ichiro 東京女子医科大学, 医学部, 講師 (80198077)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 腎臓移植 / 免疫寛容 / 移植免疫寛容 / 臓器移植

Outline of Final Research Achievements

This study was performed in kidney transplant (KTx) recipients from living donors. Lymphocytes were harvested 2 days before KTx. Recipient's PBMCs were co-cultured with irradiated (30Gy) donor cells in the presence of anti CD80/CD86 mAb for 2 weeks. As preconditioning, splenectomy or rituximab + cyclophosphamide (CP) were employed. Twelve days after KTx, the cultured cells were intravenously infused, after that immunosuppressants were gradually tapered. In the cultured cells, CD4, CD25, and FoxP3 expressions were upregulated. The recipients showed excellent graft survival rate and function. Final doses of CsA and MMF were almost half of conventional KTx, however high incidence of BPAR: 3 subclinical, 4 anti-rejection treatments, obliged us to discontinue further reducing immunosuppressants. These results showed that adoptive transfer of anergic cells could be one of promising approaches as tolerance-inducing strategy.

Research Products

• [Journal Article] A pilot study of operational tolerance with a regulatory T cell-based cell therapy in living donor liver transplantation. (2016)
  • Author(s): ①Todo S, Yamashita K, Goto R, Zaitsu M, Nagatsu A, Oura T, Watanabe M, Aoyagi T, Suzuki T, Shimamura T, Kamiyama T, Sato N, Sugita J, Hatanaka K, Bashuda H, Habu S, Demetris AJ, Okumura K
  • Journal Title: Hepatology Volume: 00 Issue: 2 Pages: 00-00
  • DOI: 10.1002/hep.28459
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Donor specific hyporesponsiveness in kidney transplantation using adoptive transfer of Ex Vivo induced tolerogenic cells (2013)
  • Author(s): 小山一郎
  • Organizer: American Transplant Congress
  • Place of Presentation: シアトル
• [Presentation] Donor specific hyporesponsiveness in kidney transplantation using adoptive transfer of Ex Vivo induced tolerogenic cells (2013)
  • Author(s): 小山一郎
  • Organizer: International Xenotransplantation Association
  • Place of Presentation: 大阪