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Evaluation of in vivo tolerogenicity of genetically modified recipient dendritic cells (syngeneic DC) pulsed with immunogenic peptides (allopeptides) derived from donor HLA molecule in HLA class I transgenic mouse.

Research Project

Project/Area Number 12671142
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionThe University of Tokyo.

Principal Investigator

BECK Yoshifumi  The University of Tokyo, Institution of Medical Science., Departments of Surgery and Bioengineering, Research Associate., 医科学研究所, 助手 (70199454)

Co-Investigator(Kenkyū-buntansha) TAHARA Hideaki  The University of Tokyo, Institution of Medical Science., Departments of Surgery and Bioengineering, Professor., 医科学研究所, 教授 (70322071)
Project Period (FY) 2000 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥2,500,000 (Direct Cost: ¥2,500,000)
KeywordsHLA / Peptide / Genetic modification / Dendritic Cell / DC / Mouse / Transplantation / Tolerance / 免疫制御 / トランスジェニックマウス / 異所性心移植モデル / HLAクラスI抗原
Research Abstract

T cells of C3H.B51 recognize HLA-B^*3501 molecules expressed on C3H.B35 as allo-MHC class I antigens and rejects vascularized C3H. B35 grafts by cellular mechanism. HLA-B^*3501 derived peptide induces long-term heart graft survival in C3H.B35 into C3H.B51 cardiac transplantation model by intra-thymic injection. (Transplant proceedings, 30, 3890-3891, 1998.) We plan to clarify the putative tolerogenic capability of DC involved with HLA molecules based on this HLA TGM heart transplant model. Application of syngeneic (recipient : C3H.B51) DC exposed to allo-antigen (HLA-B*3501 derived peptides) with some modification is expected to establish donor(C3H.B35) specific tolerance. C3H.B35 and C3H.B51 HLA transgenic mouse : So far, after several months of breeding management, the specific TGM strains have been successfully recovered from cryo-preservation. The allogeneic response, which is the key factor in this study, has been confirmed by both in vitro and in vivo study. In brief, mean survival of skin graft from C3H.B35 on C3H.B51 was 15 days and survival of heterotopic heart graft was 24 days. These findings coincides with our previous report (Ando and Beck et al., Transplantation 68, 904-908, 1999.). C3H.B35 specific cytotoxic T cell was generated from splenocytes obtained from C3H.B51 primed by C3H.B35 skin grafting and co-cultured with irradiated C3H.B35 splenocytes. The specific %lysis was more than 50% at the E : T ration of 80 : 1. DC : DC obtained from mouse bone marrow cells after removal of adherent cells followed by GM-CSF and IL4 addition showed marked allo-stimulatory effect in mixed leukocyte reaction.
We plan to investigate the possibility of regulating the allo-immune-response between the TGM strain by modified DC propagated from TGM.

Report

(3 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • Research Products

    (14 results)

All Other

All Publications (14 results)

  • [Publications] Tanaka F, Tahara, H, et al.: "Rapid generation of potent and tumor-specific cytotoxic T lymphocytes by interleukin 18 using dendritic cells and natural killer cells"Cancer Res. 60. 4838-4844 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Qin, L, Ding, Y, Tahara, H, et al.: "Viral IL-10-Induced Immunosuppression Requires Th2 Cytokines and Impairs APC Function Within the Allograft"J Immunol. 166. 2385-2393 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara, H, et al.: "Differential effects of myeloid dendritic cells retrovirally transduced to express mammalian or viral IL-10 on CTL and NK cell functions and resistance to tumor growth"Transplantation. 71. 1334-1340 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara, H, et al.: "Mammalian and Viral IL-10 Enhance C-C Chemokine Receptor 5 but Down-Regulate C-C Chemokine Receptor 7 Expression by Myeloid Dendritic Cells : Impact on Chemotactic Responses and In Vivo Homing Ability"J Immunol. 166. 7136-7143 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kishida T, Tahara, H, et al.: "In vivo electroporation-mediated transfer of interleukin-12 and interleukin-18 genes induces significant antitumor effects against melanoma in mice"Gene Ther. 8. 1234-1240 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara, H, et al.: "Retroviral delivery of transforming growth factor-β1 to myeloid dendritic cells ; inhibition of T cell priming ability and influence on allograft survival"Transplantation. (in press). (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara H, Thomson AW: "Differential effects of myeloid dendritic cells retrovirally transduced to express mammlian or viral IL-10 on CTL and NK cell activities and resistance to tumor growth"Transplantation. 71. 1334-40 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara H, Thomson AW: "Retrovirally transduced myeloid dendritic cells expressing mammalian or viral IL-10 differentially affect cellmediated immunity and growth of transplantable tumors."Transplant Proc.. 33. 590 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Morelli AE, Onai N, Hirao M, Matsushima K, Tahara H, Thomson AW: "Mammalian and viral IL-10 enhance C-C chemokine receptor 5 but downregulate C-C chemokine receptor 7 expression By myeloid dendritic cells : impact on chemotactic responses, and in vivo homing ability"J Immunol.. 166. 7136-43 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Qin L, Ding Y, Tahara H, Bromberg JS: "Viral IL-10-hiduced Immunosuppression Requires Th2 Cytokines and Impairs APC Function Within the Allograft"J Immunol. 166. 2385-2393 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Takayama T, Tahara H, et al.: "Differential effects of myeloid dendrite cells retrorirally transduced to express mamalian or viral IL-10 on CIL and NK cell activities and resistance"Transplantation. 71. 1334-1340 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayama T, Tahara H, et al.: "Refrarirally transduced myeloid cells expressing mammalian orviral IL-10 differentially affect cell mediated immunity and growth of iransplantable tumors"Transplant Proceedings. 33. 590 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Takayama T, Morelli AE, Hirao M, Matsushima K, Tahara H, Theusan AW.: "Mammalian and viral IL-10 enhance C-C chemekine receptor 5 but down-regulate C0C chemeline receptor 7 expression by myeloid dendrite cell"Journal of Immunology. 166. 7136-7143 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Qin L, Ding Y, Tahara H, et al.: "Viral IL-10 Induced immunosuppression requires Th2 cytskines and impairs APC function within the albgraftl"Journal of Immunology. 166. 2385-2393 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2000-04-01   Modified: 2016-04-21  

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