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Characterization of OX40+ T cells detected in patients with GVHD after hematopoietic stem cell transplantation

Research Project

Project/Area Number 13670454
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field 内科学一般
Research InstitutionKYOTO UNIVERSITY

Principal Investigator

HORI Toshiyuki  Kyoto University, Dept. Hematol. & Oncol., Lecturer, 医学研究科, 講師 (70243102)

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: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 2001: ¥2,400,000 (Direct Cost: ¥2,400,000)
KeywordsOX40 / OX40 ligand / gp34 / Bone marrow transplantation / GVHD / Allo reactivity / Dendritic cell / CD4 / T細胞 / GVHD / 造血幹細胞移植
Research Abstract

We studied the role of the OX40/OX40L in GVHD that is though to be ascribed to alloreactive immune response of donor-derive T cells to recipient cells.
We examined the expression of OX40 on peripheral blood T cells of post-stem cell transplantation patients after day 100. The percentages of both OX40^+CD4^+ and OX40^+CD8^+ T cells were significantly higher in patients with chronic c GVHD than those without. Serial analyses showed that OX40^+CD4^+ T cells elevated before the onset of cGVHD and at the onset closely correlated with the therapeutic response. These results indicated that serial measurement of OX40^+ T cells is useful for predicting the onset as well as therapeutic response of cGVHD and raised a possibility that the OX40/gp34 system is involved in the pathogenesis of cGVHD (Blood 98:3162, 2001). To define the role of the OX40/OX40L system in alloreactivity in more detail, we examined the effect of anti-OX40L mAb on proliferative response of CD4^+ T cells to allogeneic monocyte-derived DCs. We observed that expression of OX40 was dependent on CD28 signals and anti-OX40L mAb markedly inhibited proliferative response of CD4^+ T cells to allogeneic DC and even to sorted OX40L^- DC, indicating that the OX40/OX40L system plays a crucial role in allogeneic T cell immune response (Immunology, 109:226-231, 2003). We found that OX40 signaling induces production of RANTES at both mRNA and protein levels by vascular endothelial cells, which we first identified in screening with cDNA array (Immunol. Lett. 84:1, 2002). Now that CCR5^+ T cells are considered to initiate GVHD (Nature Immunol. 4:154, 2003), this finding may be of pathophysiological relevance.

Report

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

    (17 results)

All Other

All Publications (17 results)

  • [Publications] Ai Kotani, et al.: "Correlation of peripheral blood OX40^+ (CD134^+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation"Blood. 98. 3162-3164 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, et al.: "Singnaling of gp34 (OX40 ligand) induces vascular endothelial cells to produce a CC chemokine RANTES/CCL5"Immunol. Lett.. 84. 1-7 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akane Kunitomi, et al.: "OX40 signaling renders adult T cell leukemia cells resistant to Fas-induced apoptosis"Int. J. Hematol.. 76. 260-266 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, et al.: "Myasthenia gravis after bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40^+ CD4^+ T cells"Eur. J. Haematol.. 69. 318-320 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yumi Matsumura, et al.: "Expression of CD134 and CD134 ligand in lesional and nonlesional psoriatic skin"Arch. Dermatol. Res.. 294. 563-566 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoya Ukyo, et al.: "OX40 signaling is crucial for induction of alloreactive human T cell response"Immunology. 109. 226-231 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, Takayuki Ishikawa, Yumi Matsumura, Tatsuo Ichinohe, Hitoshi Ohno, Toshiyuki Hori, and Takashi Uchiyama: "Correlation of peripheral blood OX40+ (CD134+) T cells with chronic graft-versus-host disease in patients who underwent allogeneic hematopoietic stem cell transplantation"Blood. 66. 3162-3164 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, Toshiyuki Hori, Yumi Matsumura, and Takashi Uchiyama: "Singnaling of gp34 (OX40 ligand) induces vascular endothelial cells to produce RANTES"Immunol. Let.. 84. 1-7 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Akane Kunitomi, Toshiyuki Hori, Michiyuki Maeda and Takashi Uchiyama: "OX40 signaling renders adult T cell leukemia cells resistant to Fas-induced apoptosis"Int. J. Hematol.. 76. 260-266 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, Atsushi Takahashi, Hikari Koaga, Rinpei Morita, Hidenao Fukuyama, Tatsuo Ichinohe, Takayuki Ishikawa, Toshiyuki Hori, and Takashi Uchiyama: "Myasthenia gravis after bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX40+ CD4+ T cells"Eur. J. Hematol.. 69. 1-3 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Y. Matsumura, T. Hori, C. Nishigori, K. Shiroganel, K.-I. Toda, T. Uchiyama, Y. Tanaka and Y. Miyachi: "Expression of CD134 and CD134 ligand in lesional and nonlesional psoriatic skin"Arch. Dermatol. Res.. 294. 563-566 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Naoya Ukyo, Toshiyuki Hori, Takayuki Ishikawa, Sousi Yanagita, and Takashi Uchiyama: "OX40 signaling is crucial for induction of alloreactive human T cell response"Immunology. 109. 226-231 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Ai Kotani, et al.: "Singnaling of gp34 (OX40 ligand) induces vascular endothelial cells to produce a CC chemokine RANTES/CCL5 :"Immunol. Lett.. 84. 1-7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Akane Kunitomi, et al.: "OX40 signaling renders adult T cell leukemia cells resistant to Fas-induced apoptosis"Int. J. Hematol.. 76. 260-266 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Ai Kotani, et al.: "Myasthenia gravis after bone marrow transplantation treated with mycophenolate mofetil monitored by peripheral blood OX4O^+ CD4^+ T cells"Eur. J. Haematol.. 69. 318-320 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Naoya Ukyo, et al.: "0X40 signaling is crucial for induction of alloreactive human T cell response"Immunology. (発売予定). 226-231 (2003)

    • Related Report
      2002 Annual Research Report
  • [Publications] A.Kotani: "correlation of peripheral blood OX40^+ (CD134^+) Tcells with chronic graft-versus-host disease in patients who under went allogeneic hematopoietic stem cell transplantation"Blood. 98(10). 3162-3164 (2001)

    • Related Report
      2001 Annual Research Report

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

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