Establishmentof a strategy to regulate alloreactive T cells by CD14^+monocyte-derived endothelial-like cells for applying in organ transplantation

• Project/Area Number: 20790931
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: General surgery
• Research Institution: Hiroshima University
• Principal Investigator: TANAKA Yuka Hiroshima University, 大学院・医歯薬学総合研究科, 助教 (90432666)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2009: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2008: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 臓器移植 / 免疫寛容 / 内皮細胞

Research Abstract

We have established a strategy to inhibit alloreactive T cells without nonspecific immunosuppressants by using immune-regulatory endothelial-like cells (ELCs) derived from peripheral blood CD14^+ monocytes. We have also attempted to establish an in vivo mouse model to investigate the strategy to regulate alloreactive T cells (i.e. liver endothelia-chimeric Rag-2/γ-chain double knockout mice reconstructed with syngeneic T cells). The ELCs regenerated from peripheral blood CD14+ monocytes expressed MHC class II, CD80 and CD86 together with PDL-1 and ILT-3 (inhibitory molecules against T cells). Adding the stimulator-type ELCs into the culture of mixed reaction assay resulted in the significant inhibition of T cell proliferation in the stimulator-specific fashion. These findings suggest that adoptive transfer with the ELCs regenerated from donor peripheral blood CD14^+ monocytes specifically induces tolerance among alloreactive T cells in organ transplantation.

Research Products

• [Journal Article] Immunological property of antibodies against N-glycolylneuraminic acid epitopes in cytidine monophospho-N-acetylneuraminic acid hydroxylase-deficient mice (2010)
  • Author(s): Tahara H, Ide K, Basnet NB, Tanaka Y, Matsuda H, Takematsu H, Kozutsumi Y, Ohdan H
  • Journal Title: J Immunol 15;184(6) Pages: 3269-3275
  • Peer Reviewed
• [Journal Article] Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes (2010)
  • Author(s): Tahara H, Ide K, Basnet NB, Tanaka Y, Ohdan H
  • Journal Title: Xenotransplantation (In press)
  • Peer Reviewed
• [Journal Article] Determination of the precursor frequency and the reaction intensity of xenoreactive human T lymphocytes. (2010)
  • Author(s): Tahara H, et al.
  • Journal Title: Xenotransplantation (掲載決定)
  • Peer Reviewed
• [Presentation] 肝類洞内皮細胞の抗原特異的免疫寛容誘導能の解析 (2010)
  • Author(s): 番匠谷将孝、尾上隆司、五十嵐友香、田中友加、井手健太郎、伊禮俊充、田原裕之、田澤宏文、田代裕尊、大段秀樹
  • Organizer: 第46回日本肝臓学会総会
  • Place of Presentation: 山形
  • Year and Date: 2010-05-27
• [Presentation] Optimization of immunosuppressive therapy on the basis of immune monitoring by a multiparametric mixed lymphocyte reaction assay reduces infectious complications and mortality in living-donor liver transplantation (2010)
  • Author(s): Yuka Tanaka, Hirotaka Tashiro, Hideki Ohdan
  • Organizer: American Transplant Congress 2010
  • Place of Presentation: San Diego, USA
  • Year and Date: 2010-05-04
• [Presentation] 当院における肝移植後の免疫寛容をめざした試み～肝類洞内皮細胞の抗原特異的免疫寛容誘導能～ (2009)
  • Author(s): 番匠谷将孝
  • Organizer: 第27回日本肝移植研究会
  • Place of Presentation: 東レ総合研修センター(静岡県)
  • Year and Date: 2009-07-10