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Establishment of antigen-specific immunotherapy with artificial lymphocytes genetically engineered by antigen specific receptor and functional genes.

Research Project

Project/Area Number 11357006
Research Category

Grant-in-Aid for Scientific Research (A)

Allocation TypeSingle-year Grants
Section展開研究
Research Field 内科学一般
Research InstitutionThe University of Tokyo

Principal Investigator

YAMAMOTO Kazuhiko  The University of Tokyo, Faculty of Medicine, Professor, 医学部・附属病院, 教授 (80191394)

Co-Investigator(Kenkyū-buntansha) SAWADA Tetsuji  The University of Tokyo, Facuulty of Medicin, Assistant, 医学部・附属病院, 助手 (50235470)
DOHI Makoto  The University of Tokyo, Facuulty of Medicin, Assistant, 医学部・附属病院, 助手 (60222155)
MISAKI Yoshiikata  The University of Tokyo, Facuulty of Medicin, Lecturer, 医学部・附属病院, 講師 (60219615)
當間 重人  東京大学, 医学部・附属病院, 助手 (50207528)
Project Period (FY) 1999 – 2001
Project Status Completed (Fiscal Year 2001)
Budget Amount *help
¥38,050,000 (Direct Cost: ¥34,900,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2001: ¥13,650,000 (Direct Cost: ¥10,500,000、Indirect Cost: ¥3,150,000)
Fiscal Year 2000: ¥10,500,000 (Direct Cost: ¥10,500,000)
Fiscal Year 1999: ¥13,900,000 (Direct Cost: ¥13,900,000)
KeywordsImmune diseases / antigen-specific immunotherapy / T cell receptor / gene transduction / cell therapy / リンパ球 / レトロウィルス / T細胞クローン / レトロウイルス
Research Abstract

Antigen-specific T lymphocytes should be clonally accumulated in order to perform their roles. We have established a system to detect such accumulated T lymphocytes in a lymphocyte population using RT-PCR and SSCP method on T cell receptor (TCR). We then extended our work to reconstitute the TCR function in vitro. With this method, artificial lymphocytes for antigen-specific immunotherapy could be generated. Two technical difficulties exist. They are the pairing of two TCR messages from a single T lymphocyte and induction of multiple genes into lymphocytes from a recipient for the therapy. We have tried to develop several of these methods and found that a single cell sorting method is so far working for the pairing. Regarding the gene transfer to lymphocytes, a retrovirus vector would be the best. We have succeeded in obtaining more than 50 % of transduction of a single gene. Therefore, more than 10 % of the treated lymphocyte population could express 3 genes altogether. We are now performing experimental immunotherapy for lupus nephritis of NZB/W F1 mice using these established methods.

Report

(4 results)
  • 2001 Annual Research Report   Final Research Report Summary
  • 2000 Annual Research Report
  • 1999 Annual Research Report
  • Research Products

    (37 results)

All Other

All Publications (37 results)

  • [Publications] Yamamoto K.: "T cells and autoimmune diseases"Allergy International. 50. 1-4 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Setoguchi: "Peroxisome proliferator-activated receptor-γ haplo insufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis"J. Clin. Invest. 165. 1667-1675 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada R.: "Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihodestimation of combinatorial effect that two genetic loci have on suscepitbility to the disease"Am. J. Hum. Genet.. 68. 674-685 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki S.: "Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponstreness in mice"J. Immunol.. 166. 2055-2062 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Fujio K.: "Functional reconstitution of class II MHC-restricted T cell Immunity mediated by retroviral transfer of the αβTCR complex"J. Immunol.. 165. 528-532 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Setoguchi K.: "Antigen-spetific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen"J. Immunol.. 165. 5980-5986 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sawabe T.: "Accumulation of common clonal T cells in multiple lesions of sarcoidosis"Mol. Med.. 6. 793-802 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa M.: "Paired cloning of the T cell receptor αandβgenes from a single T cell without the establishment of a T cell clone"Clin. Exp. Immunol.. 123. 340-345 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiokawa S.: "Clonal identities and multiple sotype transcripts in hematological disease revealed by a single-strand conformation polymorphisim analysis of the immunoglobulin heavy chain messenger signals"Am. J. Hematol.. 62. 74-81 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa M.: "Frequency of clonally expanded T cells evaluated by PCR from a single cell"J. Immunol. Methods.. (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamamoto K.: "T cells and autoimmune diseases"Allergy International. 50. 1-4 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Setoguchi K., Misaki Y., Araki Y., Fujio K., Kawahata K., Kitamura T. and Yamamoto K.: "Antigen-specific T cells transduced with IL-10 ameliorate experimentally induced arthritis without impairing the systemic immune response to the antigen"J. Immunol.. 165. 5980-5986 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Setoguchi K., Misaki Y., Terauchi Y., Yamauchi T., Kawahata K., Kadowaki K. and Yamamoto K.: "Peroxisome proliferator-activated receptor-γ haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis"J.Clin. Invest.. 108. 1667-1675 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Shiokawa S., Nishimura J., Uike N., Saburi Y., Suehiro T., and Yamamoto K.: "Clonal identities and multiple isotype transcripts in hematological diseases revealed by a single-strand conformation polymorphism analysis of the immunoglobulin heavy chain messenger signals"Am.J.Hematol. 62. 74-81 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Sawabe T., Shiokawa S., Sugisaki K., Tsuda T. and Yamamoto K.: "Accumulation of common clonal T cells in multiple lesions of sarcoidosis"Mol.Med.. 6. 793-802 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa M., Furukawa H., Yabe T., Matsui M., Toda M., Hamada C., Kasukawa R., Yamamoto K., Nishioka K. and Kato T.: "Frequency of clonally expanded T cells evaluated by PCR from a single cell"J.Immunol.Methods. 224. 203-208 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Yamada R., Tanaka T., Unoki K., Nagai T., Sawada T., Ohnishi Y., Isunoda T., Yukioka M., Maeda A., Suzuki K., Tateishi H., Ochi T., Nakamura Y. and Yamamoto K.: "Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients, and maximum-likelihood estimation of combinatorial effect that two genetic loci have on susceptibility to the disease"Am.J.Hum.Genet.. 68. 674-685 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kawasaki S. Takizawa H., Yoneyama H., Nakayama T., Fujisawa R., Izumizaki M., Imai T., Yoshie O., Hommma I., Yamamoto K. and Matsushima K.: "Intervention of thymus and activation-regulated chemokine attenuates the development of allergic airway inflammation and hyperresponsiveness in mice"J.Immunol.. 166. 2055-2062 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kurokawa M., Tong J., Matsui T., Masuko-Hongo K., Yabe T., Nishikawa K., Yamamto K. Kato T.: "Paired cloning of the T cell receptor α and β genes from a single T cell without the establishment of a T cell clone"Clin.Exp.Immunol.. 123. 340-345 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2001 Final Research Report Summary
  • [Publications] Kanahata K.: "Peripheral tolerance to a nuclear autoantigen : dendritic cells expressing a nuclear autoantigen lead to persistent anergic state of CD4 autoreactive T cells after proliferation"J. Immunol.. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamamoto K.: "T cells and autoimm. disease"Allergy International. 50. 1-4 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Misaki Y.: "Game-transferred oligoclonal T cells predominantly persist in peripheral blood from on adenosine deaminase-deficient patient during gene therapy"Molcular Therapy. 3. 24-27 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hagiwara K.: "Identification of genes upregulated in the infamed colonic lesions of crohns disease"Biochem. bioph. res. co.. 283. 130-135 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yamada.R: "Association between a single-nucleotide polymorphism in the promoter of the human interleukin-3 gene and rheumatoid arthritis in Japanese patients and inaximum-likelihood estimation of combinational effect that two genetic loci have on susceptibility to the disease"Am. J. Hum. Gent. 68. 674-685 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Setoguchi K.: "Peroxisome proliferator-activated receptor-γ haploin sufficiency enhunces B cell proliferative responses and exacerbates experimentally induced arthritis"J. Clin. Invest.. 108. 1667-1675 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Misaki Y.: "Gane-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase-deficient patient during gene therapy."Molecular.Therapy. 3. 24-27 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Setoguchi K.: "Endothelin-1 is a potent activator of nonselective cation currents in human bronchial smooth muscle cells."J.Immunol.. 165. 5980-5986 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujio K.: "Functional reconstitution of class II MHC-restricted T cell immunity mediated by retroviral transfer of the αβTCR complex."J.Immunol.. 165. 528-532 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujio K.: "Molecular cloning of a novel type 1 cytokine receptor similar to the common gamma chain."Blood. 95. 2204-2210 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sasaki M.: "Accumulation of common T cell clonotype in the salivary glands of patients with human Tlymphotropic virus type I-associated and idiopathic Sjogren's syndrome."J.Immunol.. 164. 2823-2831 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Nagase H.: "Expression of CXCR4 in eosinophils : Functional analyses and cytokine-mediated regulation."J.Immunol.. 164. 5935-5943 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Matsui T. et al.: "Autoantibodies to T cell co-stimulatory molecules in systemic autoimmue diseases"J. Immunol.. 162. 4328-4335 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Furukawa H. et al.: "Splice acceptor site mutation of transporter associated with antigen processing-1 gene in human bare lymphocyte syndrome"J. Clin. Invest.. 103. 755-758 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kawahata K. et al.: "Altered expression level of a systemic nuclear autoantigen determines the fate of immune response to self"J. Immunol.. 162. 6482-6491 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Takizawa H. et al.: "Diesel exhaust particles induce NF-κB activation in human bronchial epithelial cells in vitro : Importance in cytokine transcription"J. Immunol.. 162. 4705-4711 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Miyamasu M. et al.: "Thr derived cytokine IFN-γ is a potent inhibitor of eotayin sythesis in vitro"Int. Immunol.. 11. 1001-1004 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Koshino T. et al.: "Novel polymorphism of the 5-lipoxygenase activating protein (FLAP) promoter gene associated with asthma"Mol. Cell. Bio.. 2. 32-35 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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