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The development of Autoimmune-diseases antigen-specific therapy by the induction of regulatory T cells transcription factors

Research Project

Project/Area Number 13670450
Research Category

Grant-in-Aid for Scientific Research (C)

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

Principal Investigator

MISAKI Yoshikata  The University of Tokyo, Faculty of Medicin, Lecturer, 医学部附属病院, 講師 (60219615)

Co-Investigator(Kenkyū-buntansha) YAMAGUCHI Akihiro  The University of Tokyo, Faculty of Medicin, research associate, 医学部附属病院, 助手 (90261974)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥2,200,000 (Direct Cost: ¥2,200,000)
KeywordsCD4^+CD25^+ T cells / regulatory T cells / autoimmune diseases / antigen-specific therapy / transcription factors / 自己免疫疾患 / T細胞サブセット / CD4(+)CD25(+)T細胞 / 再分化 / Th3 / Tr1
Research Abstract

CD4+CD25+ regulatory T cells control homeostasis of immune system. The decrease of this population in number has been demonstrated to result in the development of autoimmune diseases, whereas the suppression of this population has been demonstrated to elicit effective immune response to tumors. Therefore, if we are able to control the number and activity of the regulatory T cells, we may develop an innovative immunotherapy. Although we as well as others found that this population arises from self-reactive CD4+ T cells in the thymus, the precise mechanism of their development remained elusive. Since it has been demonstrated that transcription factors specific for each T helper subset are able to control the differentiation of the subsets, we decided to find transcription factors which are involved in the development of the regulatory T cells.
We conducted subtractive cDNA cloning using mRNAs from CD4+CD25+ regulatory T cells and CD4+CD25- conventional T cells. We have cloned a number of unknown cDNA clones as well as the cDNA clones corresponding to CD25, CTLA4, OX40, TLR4 and etc. those which are already known to be specific for regulatory T cells. Among the unknown clones, we have identified two cDNA clones ; the one was supposed to regulate redox and found to suppress IL-2 production and apoptosis. The other was supposed to be a transcription factor. When we overexpress this molecule in the conventional T cells, the transduced T cells stopped proliferation, suggesting that the supposed-to-be transcription factor might regulate cell proliferation or IL-2 production, both of which need to be controlled in the regulatory T cells. Due to the proliferation deficiency, we are not able to confirm their phenotype. We now con duct further investigation to reveal the mechanism of the transcription factor.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Kawahata K, Misaki Y et al.: "Generation of CD4+CD25+ regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus"J. Immunology. 168(9). 4399-4405 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y et al.: "Peripheral tolerance to a nuclear autoantigen, Dendritic cells Expressing a nuclear autoantigen lead to persistent anergic state"J. Immunology. 168(3). 1103-1112 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Setoguchi K, Misaki Y et al.: "Peroxisome proliferator-activated receptor-haploinsufficiency enhances B cell proliferative response"J. Clin. Invest. 108(11). 1667-1675 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Misaki Y, Ezaki I et al.: "Gene transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase deficient patient"Molecular Therapy. 3(1). 24-27 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto K.: "Generation of CD4^+CD25^+ regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from non-autoreactive T cells by endogenous T cell receptor expression"J. Immunol.. 168(9). 4399-4405 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto 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.. 168(3). 1103-1112 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Setoguchi K, Misaki Y, Terauchi Y, Yamauchi T, Kawahata K, Kadowaki T, Yamamoto K.: "Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis"J Clin Invest. 108(11). 1667-1675 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Misaki Y, Ezaki I, Ariga T, Kawamura N, Sakiyama Y, Yamamoto K: "Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase deficient patient during gene therapy"Molecular Therapy. 3(1). 24-27 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Kawahata K, Misaki Y et al.: "Generation of CD4^+CD25^+ Regulatory T Cells from Autoreactive T Cells Simultaneously with Their Negative Selection in the Thymus"J.Immunology. 168(9). 4399-4405 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawahata K, Misaki Y et al.: "Peripheral Tolerance to a Nuclear Autoantigen : Dendritic Cells Expressing a Nuclear Autoantigen Lead to Persistent Anergic State"J.Immunology. 168(3). 1103-1112 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Setoguchi K, Misaki Y et al.: "Peroxisome proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses"J.Clin.Invest. 108(11). 1667-1675 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Misaki Y, Ezaki I et al.: "Gene transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase deficient patient"Molecular Therapy. 3(1). 24-27 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto K: "Generation of CD4^+CD25^+regulatory T cells from autoreactive T cells simultaneously with their negative selection in the thymus and from non-autoreactive T cells by endogenous T cell receptor expression"J. Immunol. (in press).

    • Related Report
      2001 Annual Research Report
  • [Publications] Kawahata K, Misaki Y, Yamauchi M, Tsunekawa S, Setoguchi K, Miyazaki J, Yamamoto 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. 168(3). 1103-1112 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Setoguchi K, Misaki Y, Terauchi Y, Yamauchi T, Kawahata K, kadowaki T, Yamamoto K: "Peroxisome Proliferator-activated receptor-gamma haploinsufficiency enhances B cell proliferative responses and exacerbates experimentally induced arthritis"J. Uin. Invest. 108(11). 1667-1675 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Misaki Y, Ezaki I, Ariga T, Kawamura N, Sakiyama Y, Yamamoto K: "Gene-transferred oligoclonal T cells predominantly persist in peripheral blood from an adenosine deaminase deficient patient during gene therapy"Molecular Therapy. 3(1). 24-27 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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