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2000 Fiscal Year Final Research Report Summary

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)
Project Period (FY) 1998 – 2000
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.

  • Research Products

    (10 results)

All Other

All Publications (10 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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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
  • [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

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Published: 2002-03-26  

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