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MECHANISMS FOR THE INHIBITION OF DEVELOPMENT IN ENCEPHALOMYELITIS IN MICE LACKING THE EXPRESSION OF A CHEMOKINE REQUIRED FOR T CELL MIGRATION.

Research Project

Project/Area Number 10670606
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Neurology
Research InstitutionTOHO UNIVERSITY

Principal Investigator

KAKIUCHI Terutaka  TOHO UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (40126024)

Co-Investigator(Kenkyū-buntansha) NAKANO Hideki  TOHO UNIVERSITY SCHOOL OF MEDICINE, ASSOCIATE, 医学部, 助手 (30266928)
KURIHARA Teruyuki  TOHO UNIVERSITY SCHOOL OF MEDICINE, PROFESSOR, 医学部, 教授 (80098607)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1999: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1998: ¥1,600,000 (Direct Cost: ¥1,600,000)
KeywordsMultiple Sclerosis / Encephalomyelitis / EAE / T cell / Homing / plt / Chemokine / SLC / 脳脊髄膜炎
Research Abstract

We have found a mutant mouse strain with DDD background, plt (paucity of lymph node T cells) mouse, in which T cells are unable to migrate into the T cell areas in lymph nodes, Peyer's patches, or spleen white pulp. Antigen-stimulated dendritic cells do not entry into the T cell zones either. These mice lack the expression of secondary lymphoid tissue chemokine (SLC)s, which results from the deletion of SLC gene.
We examined the development of experimental allergic encephalomyelitis (EAE) in these mutant mice. When these mice were immunized with myelin basic protein (MBP), EAE developed with a fewer frequency than in the control mice. Even when the MBP-immunized mutant mice developed EAE, the clinical score in these mice was much lower than in the control mice. For further analysis, we established C57BL/6 mice with the deletion of SLC gene, and immunized with MOG35-55 peptide. C57BL/6-plt mice were also resistant to the development of EAE. MBP- or MOG-specific T cells play a critical role to develop EAE. It might be possible that these T cells were not induced in plt mice immunized with MBP or MOG. However, this possibility seems unlikely, since in vivo T cell-priming with a protein antigen was not affected in these mice. These findings suggest that a chemokine is able to control the EAE development. Our findings also raised a possibility that a chemokine might be able to control multiple sclerosis.

Report

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

    (30 results)

All Other

All Publications (30 results)

  • [Publications] Hideki Nakano et al.: "A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4"Blood. 91. 2886-2895 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Michael D. Gunn et al.: "Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization"J. Exp. Med.. 189. 451-460 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuriko Tanaka et al.: "Cholera toxin increases intracellular pH in B lymphoma cells and decreases their antigen-presenting ability"Eur. J. Immunol. 29. 1561-1570 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Akira Seo et al.: "Enhancement of B7-1 (CD80) expression of B lymphoma cells by irradiation"Immunology. 96. 642-648 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Galya Vassileva et al.: "The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine gene"J. Exp. Med.. 190. 1183-1188 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Jens V. Stein et al.: "The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function associated antigen 1-mediated arrest of rolling T lymphocytes----"J. Exp. Med.. 191. 61-75 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 垣内史堂(分担執筆): "微生物学実習提要 第2版"丸善株式会社. 369 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] 中野英樹(分担執筆): "Annual Review免疫1999"株式会社中外医学社. 329 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] H.Nakano, S.Mori, H.Yonekawa, h.Nariuchi, A.Matsuzawa, T.Kakiuchi: "A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome 4."Blood. 91. 2886-2895 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] N.Katsunuma, Y.Matsunaga, A.Matsui, H.Kakegawa, K.Endo, T.Inubuchi, T.Saibaba, Y.Ohba, T.Kakiuchi: "Novel physiological functions of cathepsin B and L on antigen processing and osteoclastic bone resorption."Advan.Enzyme Regul.. 28. 235-251 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.D.Gunn, S.Kyuwa, C.Tam, T.Kakiuchi, A.Matsuzawa, L.T.Williams, H.Nakano: "Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localization."J.Exp.Med.. 189. 451-460 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y.Tanaka, H.Nakano, F.Ishikawa, M.Yoshida, Y.Gyotoku, T.Kakiuchi: "Cholera toxin increases intracellular pH in B lymphoma cells and decreases their antigen-presenting ability."Eur.J.Immunol.. 29. 1561-1570 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Seo, F.Ishikawa, H.Nakano, H.Nakazaki, K.Kobayashi, T.Kakiuchi: "Enhancement of B7-1 (CD80) expression of B lymphoma cells by irradiation."Immunolgy. 96. 642-648 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] G.Vassileva, H.Soto, A.Zlotnik, H.Nakano, T.Kakiuchi, J.A.Hedrick, S.A.Lira: "The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes."J.Exp.Med.. 190. 1183-1188 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] A.Mabuchi, M.Kitajima-Shimizu, K.Kikuchi, Y.Nakagawa, H.Takahashi, T.Kakiuchi, K.Yokomuro: "Cultured murine parenchymal liver cells induce differentiation of bone marrow cells to macrophage-like cells which present antigen to Th1 clones but inhibit their proliferation by nitric oxide and prostaglandins."Cell.Immunol.. 196. 14-22 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] J.V.Stein, A.Rot, Y.Luo, M.Nasasimhaswamy, H.Nakano, M.D.Gunn, A.Matsuzawa, E.J.Quackenbush, M.E.Dorf, U.H.von Andrian: "The CC chemokine thymus-derived chemotactic agent 4 (TCA-4, secondary lymphoid tissue chemokine, 6Ckine, exodus-2) triggers lymphocyte function associated antigen 1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial venules."J.Exp.Med.. 191. 61-76 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Yuriko Tanaka et al.: "Cholera toxin increases intracelluclar pH in B lymphoma cells and decreases their antigen-presenting ability."Eur.J.Immunol. 29. 1561-1570 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Akira Seo et al.: "Enhancement of B7-1 (CD80) expression of B lymphoma cells by irradiation."Immunology. 96. 642-648 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Galya Vassileva et al.: "The reduced expression of 6Ckine in the plt mouse results from the deletion of one of two 6Ckine genes."J.Exp.Med.. 190. 1183-1188 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ayako Mabuchi et al.: "Cultured muring parenchymal liver cells induce differentiation of bone marrow cells to macrophage-like cells which present antigen to Thl cells out inhibit their proliferation by nitric oxide and prostaglandins"Cell.Immunol.. 196. 14-22 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Jens V.Stein et al.: "The CC chemokaine thymus-derived chemotactic agent 4(TCA-4,secondary lymphoid tissue chemokine,6Ckine,exodus-2) triggers lymphocyte function associated antigen.1-mediated arrest of rolling T lymphocytes in peripheral lymph node high endothelial vonulos."J.Exp.Med.. 191. 61-75 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] 垣内史堂: "B細胞による抗原提示とBCRシグナル"臨免疫. 32. 700-705 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Nakano H, Mori.Yonekawa, Nariuchi.Matsuzawa, et al.: "A novel mutant gene involved in T-lymphocyte-specific homing into peripheral lymphoid organs on mouse chromosome4" Blood. 91・8. 2886-2895 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] Gunn M.D., Kyuwa, Tam, Kakiuchi, Matsuzawa.et al.: "Mice lacking expression of secondary lymphoid organ chemokine have defects in lymphocyte homing and dendritic cell localezation" The Journal of Experimental Medicine. 189・3. 451-460 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Tanaka Y., Nakano, Ishikawa, Yoshida,Gyotoku, et al.: "Cholera toxin increase intracellular pH in B lymphoma cells and decrease their antigen-presenting ability" Europearn Journal of Immunology. 29(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Seo A., Ishikawa, Nakano, Nakazawa, Kobayashi.et al.: "Enhancement of B7-1(CD80)expression on B-lymphoma cells by irradiation" Immunology. 96(印刷中). (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中野英樹: "T細胞ホーミング不全遺伝子plt" 臨床免疫. 30・11. 1556-1561 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中野英樹 他: "pltマウスとケモカインSLC" Immunology Frontier. 9・1. 47-50 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] 垣内史堂(分担執筆): "微生物学実習提要" 丸善株式会社, 369 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 中野英樹(分担執筆): "Annual Review 免疫 1999" 株式会社 中外医学社, 329 (1998)

    • Related Report
      1998 Annual Research Report

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

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