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Gene therapy for autoimmune diabetes by DNA vaccine

Research Project

Project/Area Number 13660318
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Applied veterinary science
Research InstitutionYamaguchi University

Principal Investigator

HAYASHI Toshiharu  Facultyof Agriculture, Yamaguchi University, Professor, 農学部, 教授 (90111484)

Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
KeywordsTh1 / Th2 / Reovirus type-2 / Insulitis / Autoimmune diabetes / Gene therapy / ループス / インターフェロンーガンマ / IL-4 / IL-18 / IL-12 / DNAワクチン / レオウイルスー2型 / 自己免疫 / 唾液腺炎 / ラミニン / 全身性エリテマトーデス / アレルギー性気管支炎
Research Abstract

Summary consisted of 10 items listed bellow concerning gene therapy for autoimmune diabetes by DNA vaccine. (1)Th1-dominant systemic immune responses, being responsible for the development of autoimmune insulitis, might be induced by IL-12-induced and IL-18-activated mechanisms. (2)Laminin expression is associated with the cellular infiltration of the submandibular salivary gland of NZBxNZWf1 mice. (3) The reduced bronchial lesions in C57BL/6 mice were due, at least in part, to suppression of the Th2 immune response that underlies the decreased infiltration of lymphocytes and eosinophils into the bronchial mucosa. (4) Increase in serum IFN-r may be associated with the active disease in NZBxNZWF1 mice. (5) The insulitis seen in Reo-2 infection in suckling mice is induced by an immune reaction. (6) The systemic administration of IFN-r-expressing plasmid may have a modulating ability of Th1/Th2 balance to down-regulate Th2 response by mutual inhibitoru mechanisms between Th1 and Th2 cells, leading to the reduction of th LAR. (7) IFN-r but not IL-4 contribute to the development of lupus in the NZBxNZWF1 mice. (8) The IFN-r-encoding plasmid promoted autoimmune insulitis in Reo-2-induced diabetes. (9) CpG ODN may contribute to accelerate Reo-2-induced autoimmune reaction against pancreatic islet cells via additional effects of Th1 cytokine especially IFN-r. (10) ICAM-1/LFA-1 may be required for the differentiation of Th0 cells to Th1 cells, which mediate insulitis with IGT in Reo-2-infected suckling mice.

Report

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

    (29 results)

All Other

All Publications (29 results)

  • [Publications] Hayashi T. et al.: "Possible involvement of IL-12 in reovirus type-2-induced Diabetes in newborn DBA/1 mice"Scand.J.Immuno.. 53. 572-578 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., Shirachi T., Hasegawa K.: "Relationship between sialoadenitis and periductal laminin expression in submandibular gland of NZBxNZWf1mice"J. Comp. Path.. 125. 110-116 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., Hasegawa K, et al.: "Bronchial lesions of the late asthmatic response in BALB/c and C57BL/6 mice"J. Comp. Path.. 83. 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] Hayashi T., Hasegawa K, et al.: "Reduction of serum IFN-r concentration and lupus development in NZBxNZWF1 mice by LDV infection"J. Comp. Path.. 125. 285-291 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T. et al.: "Systemic administration of histamine reduces reovirus type-2-induced insulitis in suckling DBA/1 mice"J. Comp. Path.. 126. 153-160 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T. et al.: "Systemic administration of IFN-r-expressing plasmid reduces the late allergic bronchitis in a mouse model of asthma"Int. J. Exp. Path.. 83. 1-6 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa K., et al.: "Promotion of lupus in NZBxNZWF1 mice by plasmids encoding IFN-r, but not by those encoding IL-4"J. Comp. Path.. 127. 203-207 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa K., et al.: "Plasmid encoding IFN-r exacerbates reovirus type-2-induced diabetes in DBA/1 suckling mice"J. Comp. Path.. 127. 1-6 (2002)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., et al.: "CpG ODN accelerate reovirus type 2-induce insulitis in DBA/1 suckling mice"Int. J. Exp. Path.. 83. 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] Hayashi T., et al.: "Effect of antibodies to ICAM-1 and LFA-1 on cytokaine mRNA expression in reovirus type-2-triggered autoimmune"J. Comp. Path.. 128. 283-288 (2003)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., et al.: "Possible involvement of IL-12 in reovirus type-2-induced diabetes in newborn DBA/1 mice"Scand. J. Immuno.. 53. 572-578 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., Shirachi T., Hasegawa K.: "Relationship between sialoadenitis and periductal laminin expression in submandibular gland of NZBxNZWf1 mice"J. Comp. Path.. 125. 110-116 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., Hasegawa K., et al.: "Bronchial lesions of the late asthmatic response in BALB/c and C57BL/6 mice"J. Comp. Path.. 125. 208-213 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., Hasegawa K., et al.: "Reduction of serum IFN-r concentration and lupus development in NZBxNZWF1 mice by LDV infection"J. Comp. Path.. 125. 285-291 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., et al.: "Systemic administration of histamine reduces reovirus type-2-induced insulitis in suckling DBA/1 mice"J. Comp. Path.. 126. 153-160 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., et al.: "Systemic administration of IFN-r-expressing plasmid reduces the late allergic bronchitis in a mouse model of asthma"Int. J. Exp. Path. 83. 1-6 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa K., et al.: "Promotion oflupus in NZBxNZWF1 mice by plasmids encoding IFN-r but not by those encoding 1L-4"J. Comp. Path.. 127. 203-207 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa K., et al.: "Plasmid encoding IFN-r exacerbates reovirus type-2-induced dia betes in DBA-1 suckling mice"J. Comp. Path.. 127. 1-6 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hayashi T., et al.: "CpG ODN accelerate reovirus type 2- induced insulitis in DBA/1 suckling mice"Int. J. Exp. Path.. 83. 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] Hayashi T., et al.: "Effect of antibodies to ICAM-1 and LFA-1 on cytokine mRNA expression in reovirus type-2-triggered autoimmune insulitis in DBA/1 suckling mice"J. Comp. Path.. 128. 283-288 (2003)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Hasegawa K., Hayashi T.et al.: "Promotion of lupus in NZBxNZWF_1 mice by plasmids encoding interferon (IFN)-γ but not by those encoding interleukin (IL)-4"J. Comp. Path.. 126. 1-6 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayashi T., Yoshinaka K., Hasegawa K.et al.: "CpG Oligodeoxynucleotides accelerate reovirus type-2 triggered insulitis in DBA・1 suckling mice"Int. J. Exp. Path.. 83. 1-7 (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayashi T., Hasegawa K.et al.: "Effect of antibodies to ICAM-1 and LFA-1 on cytokine mRNA expression in reovirus type-2-triggered autoimmune insulitis in suckling DBA/1 mice"J. Comp. Path.. (In press). (2002)

    • Related Report
      2002 Annual Research Report
  • [Publications] Hayashi, T. et al.: "Possible involvement of IL-12 in reovirus type-2-induced diabetes in newborn DBA/1 mice."Scand. J. Immunol.. 53. 1-8 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hyashi, T., Shirach, T., Hasegawa, K.: "Relationship between sialoadenitis and periductal laminin expression in submandibular salivary gland of NZBxNZWF1 mice"J. Comp. Path.. 125. 208-213 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi, T., Hasegawa, K., Nakai, S., et al.: "Bronchial lesions of the late asthmatic response in BALB/c and C57BL/6 mice"J. Comp. Path.. 125. 208-213 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi, T., Hasegawa, K., Ohta, A., Maeda, K.: "Suppression of age-associated increase in IFN-r in the blood during chronic LDV infection in NZBxNZWF1 mice."J. Comp. Path.. 125(In press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi T., Anayama, H., Hasegawa, K., Iwata, H., 0nodera, T: "Systemic adnministration of histamine prevents reovirus type 2-induced diabetes in newborn mice."J. Comp. Path.. 125(In press). (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Hayashi, T., Maeda, K., Hasegawa, K., Nakai, S., Hamachi, T., Iwta, H.: "Interferon-r expressing-plasmid DNA reduces late allergic bronchitis in a Mouse model of asthma"Int. J. Exp. Path.. (In peess). (2002)

    • Related Report
      2001 Annual Research Report

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

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