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Regulation of infectious immunity by the OX40-0X4OL system

Research Project

Project/Area Number 13226006
Research Category

Grant-in-Aid for Scientific Research on Priority Areas

Allocation TypeSingle-year Grants
Review Section Biological Sciences
Research InstitutionTohoku University

Principal Investigator

SUGAMURA Kazuo  Tohoku Univ, Grad Sch of Med, Professor, 大学院・医学系研究科, 教授 (20117360)

Co-Investigator(Kenkyū-buntansha) ISHII Naoto  Tohoku Univ, Grad Sch of Med, Associate Professor, 大学院・医学系研究科, 助教授 (60291267)
Project Period (FY) 2001 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥68,600,000 (Direct Cost: ¥68,600,000)
Fiscal Year 2005: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2004: ¥16,500,000 (Direct Cost: ¥16,500,000)
Fiscal Year 2003: ¥17,600,000 (Direct Cost: ¥17,600,000)
Fiscal Year 2002: ¥18,000,000 (Direct Cost: ¥18,000,000)
KeywordsOX40 (CD134) / Inflammatory bowel disease / Linkage analysis / OX40(CD134) / NK細胞 / T細胞 / 炎症反応 / エフェクターT細胞 / T細胞補助シグナル / OX40 / OX40リガンド / L.major / サイトメガロウイルス / ウイルス / 免疫記憶 / サイトカイン / 寄生虫 / OX40リガンド(OX40L) / OX40L遺伝子欠損マウス / OX40L遺伝子導入マウス / Leishmania major
Research Abstract

OX40-0X4OL interactions regulate survival and homeostasis of CD4+ T cells. Furthermore, several reports have demonstrated that OX40 signaling in T cells mediates not only autoimmune/inflammatory responses, but also infectious immunity by regulating T cell immunity. Interestingly, C57BL/6 OX40L-transgenic mice, which were constructed by using mouse lck proximal promoter, showed susceptibility to L. major infection although C57BL/6 wild-type mice are resistant to the infection. Since IL-13-deficiency in OX40L-transgenic mice recovered the susceptibility, IL-13 production induced by OX40 signals may mediates the susceptibility to L. major infection. In addition, OX40L-transgenic mice spontaneously develop organ-specific immune-associated diseases, namely interstitial pneumonia and inflammatory bowel disease (IBD). Studies using the OX40L-transgenic mice have demonstrated that OX40 signaling prominently affected the sensitivity of T cells to CD25+ regulatory-T-cell-mediated suppression, leading to IBD. Further investigation revealed that the development of IBD requires intestinal bacterial flora. Interestingly, IBD develops in a C57BL/6 strain-dependent manner. Thus, we have attempted to identify susceptibility genes for IBD seen in OX40L-Tg mice. A QTL analysis using the susceptible strain (C57BL/6) and a resistant strain (BALB/c) revealed a susceptibility locus on Ch. 4, which is syntenic to a human IBD-susceptibility locus (IBD7). These results suggest that a certain gene in this locus contributes to IBD development, which is associated with intestinal immunity to the bacterial flora.

Report

(6 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • 2002 Annual Research Report
  • 2001 Annual Research Report
  • Research Products

    (39 results)

All 2006 2005 2004 Other

All Journal Article (22 results) Publications (17 results)

  • [Journal Article] OX40-OX40L interaction through T cell-T cell contact contributes to CD4 T cell longevity2006

    • Author(s)
      Pejman Soroosh
    • Journal Title

      J. Immunol (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Important role of endogenous Erythropoietin system to recruit endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice.2006

    • Author(s)
      佐藤 公雄
    • Journal Title

      Circulation (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Regulatory T cell-like activity of <Foxp3^+> adult T-cell leukemia cells.2006

    • Author(s)
      陳書明 (Shumign Chen)
    • Journal Title

      Int. Immunol 18

      Pages: 269-277

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] OX40-0X4OL interaction through T cell-T cell contact contributes to CD4 T cell longevity2006

    • Author(s)
      Soroosh P et al.
    • Journal Title

      J. Immunol. 176

      Pages: 5975-87

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Important role of endogenous Erythropoietin system to recruit endothelial progenitor cells in hypoxia-induced pulmonary hypertension in mice.2006

    • Author(s)
      Satoh K et al.
    • Journal Title

      Circulation 113

      Pages: 1442-50

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Regulatory T cell-like activity of Foxp3+ adult T-cell leukemia cells.2006

    • Author(s)
      Chen S, et al.
    • Journal Title

      Int. Immunol. 18

      Pages: 269-277

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] OX40-OX40L interaction through T cell-T cell contact contributes to CD4 T cell longevity2006

    • Author(s)
      Pejman Soroosh
    • Journal Title

      J.Immunol (印刷中)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Regulatory T cell-like activity of Foxp3^+ adult T-cell leukemia cells.2006

    • Author(s)
      陳書明(Shumign Chen)
    • Journal Title

      Int.Immunol 18

      Pages: 269-277

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.2005

    • Author(s)
      Nimura A
    • Journal Title

      J. Virol. 79

      Pages: 11925-34

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of <CD8^+> memory T cells and their capacity for secondary expansion.2005

    • Author(s)
      Hendriks J
    • Journal Title

      J. Immunol 175

      Pages: 1665-1676

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.2005

    • Author(s)
      Wang X
    • Journal Title

      Nature Genet 37

      Pages: 365-372

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Annual Research Report 2005 Final Research Report Summary
  • [Journal Article] Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.2005

    • Author(s)
      Nimura A, et al.
    • Journal Title

      J. Krol 79

      Pages: 11925-34

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8+ memory T cells and their capacity for secondary expansion.2005

    • Author(s)
      Hendriks, J, et al.
    • Journal Title

      J. Immunol. 175

      Pages: 1665-1676

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Positional identification of TNFSF4, encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.2005

    • Author(s)
      Wang, X, et al.
    • Journal Title

      Nat. Genet. 37

      Pages: 365-372

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Aberrant activation of the interleukin-2 autocrine loop through the nuclear factor of activated T cells by nonleukemogenic human T-cell leukemia virus type 2 but not by leukemogenic type 1 virus.2005

    • Author(s)
      Nimura, A
    • Journal Title

      J.Virol. 79

      Pages: 11925-11934

    • Related Report
      2005 Annual Research Report
  • [Journal Article] During viral infection of the respiratory tract, CD27, 4-1BB, and OX40 collectively determine formation of CD8^+ memory T cells and their capacity for secondary expansion.2005

    • Author(s)
      Hendriks, J
    • Journal Title

      J.Immunol 175

      Pages: 1665-1676

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Hrs, a mammalian master molecule in vesicular transport and protein-sorting, suppresses the degradation of ESCRT proteins STAM1 and STAM2.2005

    • Author(s)
      Kobayashi H, Sugamura K.ほか
    • Journal Title

      J.Biol.Chem (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Positional identification of TNFSF4,encoding OX40 ligand, as a gene that influences atherosclerosis susceptibility.2005

    • Author(s)
      Wang, X., Ishii, N., Sugamura, K.ほか
    • Journal Title

      Nat.Genet (印刷中)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Distinct roles for the OX40-OX40L interaction regulatory and non-regulatory T cells.2004

    • Author(s)
      Takeda, I., Ishii, N., Sugamura K.ほか
    • Journal Title

      J.Immunol. 172

      Pages: 3580-3589

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Adenovirus vector-mediated in vivo gene transfer of OX40 ligand to tumor cells enhances anti-tumor immunity of tumor-bearing hosts.2004

    • Author(s)
      Andarini, S., Ishii, N., Sugamura, K.ほか
    • Journal Title

      Cancer Res. 64

      Pages: 3281-3287

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Therapeutic targeting of the effector T cell costimulatory molecule OX402004

    • Author(s)
      Sugamura, K., Ishii, N., Weinberg, A.D
    • Journal Title

      Nat.Rev.Immunol. 4

      Pages: 420-431

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Expanding role of T-cell costimulators in regulatory T-cellfunction : recent advances in accessory molecules expressed onboth regulatory and non-regulatory T cells.2004

    • Author(s)
      Ndhlovu, L.C., Ishii, N., Sugamura K.ほか
    • Journal Title

      Crit.Rev.Immunol 24

      Pages: 251-266

    • Related Report
      2004 Annual Research Report
  • [Publications] Takeda, I., Murata, K., Killeen, N., Ndhlovu, L.C., Satomi, S., Sugamura, K., Ishii, N.: "Distinct roles for the OX40-OX40L interaction in regulatory and non-regulatory T cells."J.Immunol. 172. 3580-3589 (2004)

    • Related Report
      2003 Annual Research Report
  • [Publications] Ishii, N., Ndhlovu, L.C., Murata, K., Sato, T., Kamanaka, M., Sugamura, K.: "OX40(CD134) and OX40 ligand interaction plays an adjuvant role during in vivo Th2 responses."Eur.J.Immunol.. 33. 2372-2381 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kanazawa, C., Morita, E., Yamada, M., Ishii, N., Miura, S., Asao, H., Yoshimori, T., Sugamura, K.: "Effects of deficiencies of STAMs and Hrs, mammalian class E Vps proteins, on receptor downregulation."Bioch.Biophys.Res.Comm.. 309. 848-856 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Kikuchi, K., Ishii, N., Asao, H., Sugamura, K.: "Identification of AMSH-LP containing a Jab/MPN domain metalloenzyme motif."Bioch.Biophys.Res.Comm.. 306. 637-743 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Hoshino, A., Tanaka, Y., Akiba, H., Asakura, Y., Mita, Y., Sakurai, T., Takaoka, A., Nakaike, S., Ishii, N., Sugamura, K., Yagita, H., Okumura, K.: "Critical role, for OX40 ligand in the development of pathogenic Th2 cells in a murine model of asthma."Eur.J.Immunol.. 33. 861-869 (2003)

    • Related Report
      2003 Annual Research Report
  • [Publications] Chisaka, H., Morita, E., Murata, K., Ishii, N., Yaegashi, N., Okamura, K., Sugamura, K.: "A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19"J Gen Virol.. 83. 273-281 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Tateyama, M., Fujihara, K., Ishii, N., Sugamura, K., Onodera, Y., Itoyama, Y.: "Expression of OX40 in muscles of polymyositis and granulomatous myopathy"J.Neurol.Sci.. 194. 29-34 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Murata, K., Nose, M., Ndhlovu, L.C., Sato, T., Sugamura, K., Ishii, N: "Constitutive OX40/OX40 ligand interaction induces autoimmune-like diseases"J.Immunol.. 169. 4628-4636 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Sato, T., Ishii, N., Murata, K., Kikuchi, K., Nakagawa, S., Ndhlovu, L.C., Sugamura K: "Consequences of OX40-OX40 ligand interactions in Langerhans cell function : Enhanced contact hypersensitivity responses in OX4OL transgenic mice"Eur.J.Immunol.. 32. 3326-3335 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Yamada, M., Ishii, N., Asao, H., Murata, K., Kanazawa, C., Sasaki, H., Sugamura, K: "Signal transducing adaptor molecules STAM1 and STAM2 are required for T-cell development"Mol.Cell.Biol.. 22. 8648-8658 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hoshino, A., Tanaka, Y., Akiba, H., Asakura, Y., Mita, Y., Sakurai, T., Takaoka, A., Nakaike, S., Ishii, N., Sugamura, K., Yagita, H., Okumura, K: "Critical role for OX40 ligand in the development of pathogenic Th2 cells in a murine model of Asthma"Eur.J.Immunol. (印刷中).

    • Related Report
      2002 Annual Research Report
  • [Publications] Chisaka, H., et al.: "A transgenic mouse model for non-immune hydrops fetalis induced by the NS1 gene of human parvovirus B19"J.Gen.Virol. 83. 273-281 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Yagi, K. et al.: "c-myc is a downstream target of the Smad pathway"J.Biol.Chem.. 277. 854-861 (2002)

    • Related Report
      2001 Annual Research Report
  • [Publications] Morita, E., et al.: "Human parvovirus B19 induces cell cycle arrest at G2 phase with accumulation of mitotic cyclins"J.Virol. 75. 7555-7563 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ishii, N., et al.: "Loss of neuron in the hippocampus and cerebral cortex of AMSH-deficient mice"Mol.Cell.Biol. 21. 8626-8637 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Ndhlovu, L.C., et al.: "Critical involvement of OX40 ligand signals in the T-cell priming events during experimental autoimmune encephalomyelitis"J.Immunol. 167. 2991-2999 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Baba, E. et al.: "Functional CD4 T cells after intercellular molecular transfer of OX40 ligand"J.Immunol. 167. 875-883 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2002-04-01   Modified: 2018-03-28  

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