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APPROACHES FOR CONTROLLING INFECTION BY GENE THERAPY

Research Project

Project/Area Number 10044299
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionEHIME UNIVERSITY

Principal Investigator

ASANO Yoshihiro  EHIME UNIVERSITY, SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (70114353)

Co-Investigator(Kenkyū-buntansha) KUBO Shuichi  TOKYO METROPOLITAN MEDICAL RESEARCH INSTITUTE RESEARCH FELLOW, 研究員 (00251223)
NAKAYAMA Toshinori  CHIBA UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (50237468)
SHINOMIYA Hiroto  EHIME UNIVERSITY, SCHOOL OF MEDICINE, ASSOCIATE PROFESSOR, 医学部, 助教授 (80162618)
ALFRED Singer  米国国立癌研究所, 実験免疫部門, 部門長
RICHARD J. Hodes  米国国立加齢医学研究所, 所長
SINGER Alfre  米国国立癌研究所, 実験免疫部門, 部門長
HODES Richar  米国国立加齢医学研究所, 所長
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥7,600,000 (Direct Cost: ¥7,600,000)
Fiscal Year 2000: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥2,800,000 (Direct Cost: ¥2,800,000)
Keywordsinfection immunity / innate immunity / T cell subset / IL-12 p40 / macrophage function
Research Abstract

Successful development of Th2 cells requires both differentiation and expansion processes, and depends on the activation levels of IL-4 receptor (IL-4R) -mediated signaling. Among signaling molecules downstream of IL-4R, STAT6 activation is thought to be critical for differentiation process, and phosphorylation of IRS-2 is important for proliferation. The activation of Ras/MAPK cascade appears to act on Jak1 kinase to enhance its kinase activity and improve IL-4R function. The activation of CN in naive CD4 T cells induces transcriptional upregulation of Jak3. STAT5 is found to be physically and functionally associated with IL-4 receptor complex in the anti-TCR-activated naive T cells and established cloned Th2 cells. The IL-4-induced activation of STAT5 appears to play an important role in the expansion process of the developing Th2 cells. Thus, the recruitment of Jak3 and STAT5 molecules to functional IL-4R complex in developing Th2 cells appears to be crucial for Th2 cell development.
We demonstrated that the splenomegaly associated with Salmonella-infection, a host-defensive response, was caused by the migration of Mac-1^+ cells into the infected spleen. We tried to generate murine bone marrow-derived DC lines by using a helper-free and replication-defective recombinant retrovirus encoding the SV40 early antigens, and obtained several DC lines that can cytokine-independently grow.
We established the mutant Listeria monocytogenes which expressed ply118 gene product when virulence genes are activated. We tried to establish the gene transduction system using this mutant Listeria.

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (25 results)

All Other

All Publications (25 results)

  • [Publications] Feng,C.: "An alternate pathway for type 1 T cell differentiation."Int.Immunol.. 11. 1185-1194 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kubo,M.: "T cell receptor stimulation and CD28 costimulation increases IL-4 receptor sensitivity : A requirement for Th2 differentiation."J.Immunol.. 163. 2432-2442 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tan,S-P.: "Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice against Plasmodium berghei ANKA blood-stage malaria infection."Parasit Immunol.. 22. 425-435 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimoda,K.: "Tyk2 plays a restricted role in IFNγ signaling although it is required for IL-12-mediated T cell function."Immunity. 13. 561-571 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tan, R.S-P., A.U.Kara, C.Feng, and Y.Asano: "Nitoric oxide is not essential in the protection of Plasmodium berghei blood stage murine malaria infection in IRF-1 (interferon regulatory factor-1) deficient mice."9th International Congress of Parasitology, eds., Tada, I., Kojima, S., and Tsuji, M., Monduzzi Editore, Italy. 1003-1007 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tan, R.S-P., C.Feng, Y.Asano, and A.U.Kara: "Altered immune response of interferon regulatory factor-1 deficient (IRF-1^<-/->) mice against Plasmodium berghei blood stage malaria infection."Infect.Immuity. 67. 2277-2283 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Watanabe, T., T.Inoue, H.Ochi, M.Terashima, Y.Asano, and T.Nakatani: "Lipid A directly inhibits IL-4 production by murine Th2 cells but does not inhibit IFN-γproduction by Th1 cells."Eur.J.Immunol.. 29. 413-418 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Feng, C., S.Watanabe, S.Maruyama, G.Suzuki, M.Sato, T.Furuta, S.Kojima, S.Taki, and Y.Asano: "An alternate pathway for type 1 T cell differentiation."Int.Immunol.. 11. 1185-1194 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] M.Shinomiya, S.M.F.Akbar, H.Shinomiya and M.Onji: "Transfer of dendritic cells ex vivo stimulated with IFN-γ down-modulates autoimmune diabetes in non-obese (NOD) mice."Clin.Exp.Immunol.. 117. 38-43 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shimoda, K., Kato, K., Aoki, K., Matsuda, T., Miyamoto, A., Shibamori, M., Yamashita, M., Numata, A., Takase, K., Kobayashi, S., Shibata, S., Asano, Y., Gondo, H., Sekiguchi, K., Nakayama, K., Nakayama, T., Okamura, T., Okamura, S., Niho, Y., and Nakayama, K.: "Tyk2 plays a restricted role in IFNγ signaling although it is required for IL-12-mediated T cell function."Immunity. 13. 561-571 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Feng,C.: "An alternate pathway for type 1 T cell differentiation."Int.Immunol.. 11. 1185-1194 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Kubo,M.: "T cell receptor stimulation and CD28 costimulation increases IL-4 receptor sensitivity : A requirement for Th2 differentiation."J.Immnol.. 163. 2432-2442 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tan,S-P.: "Differential interleukin-10 expression in interferon regulatory factor-1 deficient mice against Plasmodium berghei ANKA blood-stage malaria infection."Parasit Immunol.. 22. 425-435 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shimoda,K.: "Tyk2 plays a restricted role in IFNγ signaling although it is required for IL-12-mediated T cell function."Immunity. 13. 561-571 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Tan,R.S-P.: "Altered immune response of interferon regulatory factor-1 deficient (IRF-1-/-)mice against Plasmodium berghei blood stage malar"Infect.Immunity. 67. 2277-2283 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 浅野喜博: "IRF-1と感染制御"感染・炎症・免疫. 29. 162-169 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Feng,C: "An alternate pathway for type 1 T cell differentiation."Int.Immunol.. 11. 1185-1194 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 浅野喜博: "自然免疫系と獲得免疫系の接点"愛媛医学. 18. 507-515 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Watanabe,T.: "Lipid A directly inhibits IL-4 production by murine Th2 cells but does not inhibit IFN-γ production by Th1 cells."Eur.J.Immunol.. 29. 413-418 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tan,R.S-P.: "Altered immune response of interferon regulatory factor-1 deficient(IRF-1-/-)mice against Plasmodium terghet blood stane malaria lafection" Infect.Immunity(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] 浅野喜博: "IL-12に依存しないTh1細胞への分化" 臨床免疫(印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] 馮 熾光: "IRF-1によるTh細胞分化制御" 免疫1998-'99. 158-165 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Shinomiya,M.: "Transfer of dendritic cells ex vivo stimulated with interferon-gamma down-modulates diabetes in nonobese diabetic mice." Clinical and Experimental Immunology. (印刷中).

    • Related Report
      1998 Annual Research Report
  • [Publications] Yamashita,M.: "Requirement for p56(lck)tyrosine kinase activation in Th subset differentiation." Int Immunol.10(5). 577-591 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Hasegawa,A.: "Regulation of T cell autoreactivity to MHC class II by controlling CD80 (B7-1)expression on B cells." Int Immunol.10(2). 147-158 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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