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2002 Fiscal Year Final Research Report Summary

Functional analysis of the non-HLA genes within major histocompatibility complex (MHC) region with the use of gene-targeted mice

Research Project

Project/Area Number 13670320
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionUniversity of Tokushima

Principal Investigator

MATSUMITO Mitsuru  Institute for Enzyme Research, Professor, 分子酵素学研究センター, 教授 (60221595)

Co-Investigator(Kenkyū-buntansha) MATSUSHIMA Akemi  Institute for Enzyme Research, Lecturer, 分子酵素学研究センター, 教務員 (70116862)
Project Period (FY) 2001 – 2002
KeywordsLymphotoxin receptor / Signal transduction / NF-Kb / NIK / T cell
Research Abstract

NF-Kb-inducting kinase (NIK) is involved in lymphoid organogenesis in mice through lymphotoxin-b receptor signaling. To clarify the roles of NIK in T cell activation through TCR/CD3 and co atimulation pahways, we have studied the function of T cells from aly mice, a strain with mutant NIK. NIK mutant T cells showed impaired proliferation and IL-2 production in respones to anti-CD3 stim ulation, and these effects were caused by impaired NF-Kb activity in both mature and immature T cells; the impaired NF-Kb. In contrast, responses to co- stimulatory signals were largely retained in aly mice, suggesting that NIK is not uniquely coupled to the co-stim ulatory pathways. When NIK mutant T cells were stimulated in the presence of a protein kinase C (PKC) inhibitor, proliferative responses were abrogated more severely than in control mice, suggesting that both NIK and PKC control T cell activation in a cooperative manner. We also demonstrated that NIK and PKC are involved in distinct NF-Kb activation pathways downstream of TCR/CD3. These results suggest critical roles for NIK in setting the threshold for T cell activation, and partly account for the immunodeficiency in aly mice.

  • Research Products

    (4 results)

All Other

All Publications (4 results)

  • [Publications] Matsumoto, M., et al.: "Essential role of NF-κB-inducing kinase in T cell activation through the TCR/CD3 pathway"Journal of Immunology. 169. 1151-1158 (2002)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsushima, A., et al.: "Essential role of NF-κB-inducing kinase and IκB-kinase α in NF-κB activation through lymphotoxin-β receptor, but not through TNF receptor-I"Journal of Experimental Medicine. 193. 631-636 (2001)

    • Description
      「研究成果報告書概要(和文)」より
  • [Publications] Matsumoto,M, et al.: "Essential role of NF-Kb-inducing kinase in T cell activation through the TCR/CD3 pathway"Journal of Immunology. 169. 1151-1158 (2002)

    • Description
      「研究成果報告書概要(欧文)」より
  • [Publications] Matsushima,A, et al.: "Essential role of NF-Kb-inducing kinase and IkB-kinase a in NF-Kb activation through lymphotoxin-B receptor, but not through TNF receptor-I"Journal of Experimental Medicine. 193. 631-636 (2001)

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2004-04-14  

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