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Immune regulation by OX40/OX40 ligand system

Research Project

Project/Area Number 11670311
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionTohoku University

Principal Investigator

ISHII Naoto  Graduate School of Medicine, Tohoku University, Research Associate, 大学院・医学系研究科, 助手 (60291267)

Co-Investigator(Kenkyū-buntansha) ASAO Hironobu  Graduate School of Medicine, Tohoku University, Associate Professor, 大学院・医学系研究科, 助教授 (80250744)
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2000: ¥1,800,000 (Direct Cost: ¥1,800,000)
Fiscal Year 1999: ¥1,800,000 (Direct Cost: ¥1,800,000)
KeywordsOX40 ligand / OX40L-deficient mice / Experimental autoimmune encephalomyelitis (EAE) / Leishmania Major感染症 / OX40 / 抗原提示細胞
Research Abstract

OX40 expressed on activated T cells is known to be an important costimulatory molecule on T cell activation in vitro. However, the in vivo functional significance of the interaction between OX40 and its ligand, OX40L is still unclear. To investigate the role of OX40L during in vivo immune responses, we generated OX40L-deficient mice and a blocking anti-OX40L mAb, MGP34. OX40L expression was demonstrated on splenic B cells after CD40 and anti-IgM stimulation, while only CD40 ligation was capable of inducing OX40L on dendritic cells. OX40L-deficient and MGP34-treated mice, engendered apparent suppression of the recall reaction of T cells primed with both protein- and allo-antigens and a significant reduction in KLH-specific IgG production. The impaired T-cell-priming was also accompanied by a concomitant reduction of both Th1 and Th2 cytokines. Furthermore, antigen presenting cells (APCs) derived from the mutant mice revealed an impaired intrinsic APC function, demonstrating the importance of OX40L in both the priming and effector phases of T cell activation. Collectively, these results provide convincing evidence that OX40L, expressed on APCs, plays a critical role in antigen-specific T cell responses in vivo.
Furthermore, we examined the effect of OX40L-deficiency or blockade of OX40-OX40L interaction in pathogenesis of experimental autoimmune encephalitis (EAE), which is a mouse model for human multiple sclerosis. OX40L-deficient and MGP34-treated mice showed less symptoms and rapid recovery during EAE as compared with wild type or control Ab-treated mice. These results suggest that OX40L may be functionally involved in the pathogenesis of autoimmune diseases such as EAE.

Report

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

    (10 results)

All Other

All Publications (10 results)

  • [Publications] Onodera J,Nagata T,Fujihara K,Ohuchi M,Ishii N, et al.: "Expression of OX40 and OX40 ligand (gp34) in the normal and myasthenic thymus."Acta Neurol Scand.. 102・4. 236-243 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murata,K.,Ishii,N.,Takano,H. et.al.: "Impairment of antigen presenting cell function in mice lacking expression of OX40 ligand."J.Exp.Med.. 191・2. 365-374 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Onodera J, Nagata T, Fujihara K, Ohuchi M, Ishii N, Sugamura K, and Itoyama Y.: "Expression of OX40 and OX40 ligand (gp34) in the normal and mvasthenic thvmus"Acta Neurol Scand.. Vol.102. 236-243 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Murata, K., Ishii, N., Takano, H., Miura S, Nodhlovu LC, Nose M, Noda T, and Sugamura K.: "Impairment of antigen presenting cell function in mice lacking expression of OX40 ligand."J.Exp.Med.. Vol.191. 365-374 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Yamada M,Takeshita T,Miura S,Kimura Y,Ishii N, et al.: "Loss of hippocampal CA3 pyramidal neurons in mice lacking STAM1"Mol.Cel.Biol.,. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kikuchi K,Kawasaki Y,Ishii N, et al.: "Suppression of thymic development by the dominant-negative form of Gads"Int.Immunol.,. (in press). (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kumaki S,Ishii N,Minegishi M, et al.: "Characterization of the gammac chain among 27 unrelated Japanese patients with X-linked severe combined immunodeficiency (X-SCID)."Hum Genet.. 107・4. 406-408 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Onodera J,Nagata T,Fujihara K,Ohuchi M,Ishii N, et al.: "Expression of OX40 and OX40 ligand (gp34) in the normal and myasthenic thymus"Acta Neurol Scand.. 102・4. 236-243 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Murata,K.,Ishii,N.,Takano,H., et. al.: "Impairment of antigen presenting cell function in mice lacking expression of OX40 ligand."J.Exp.Med.. 191・2. 365-374 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kazuko Murata et.al.: "Impairment of Antigen-presenting Cell Function in Mice Lacking Expression of OX40 Ligand"J. Exp. Med.. 191. 365-374 (2000)

    • Related Report
      1999 Annual Research Report

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

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