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Development and physiological role of gammadeltaT cells.

Research Project

Project/Area Number 07044293
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research InstitutionKeio University

Principal Investigator

ISHIKAWA Hiromichi  Sch.of Med.Keio University, Assoc.Prof., 医学部, 助教授 (20051667)

Co-Investigator(Kenkyū-buntansha) ITOHARA Shigeyoshi  Kyoto University, Sch.Med., Assoc.Prof., ウイルス研究所, 助教授 (60252524)
TONEGAWA Susumu  MIT,Prof., 生物学教室, 教授
Project Period (FY) 1995
Project Status Completed (Fiscal Year 1995)
Budget Amount *help
¥8,700,000 (Direct Cost: ¥8,700,000)
Fiscal Year 1995: ¥8,700,000 (Direct Cost: ¥8,700,000)
KeywordsgammadeltaT Cells / gammadelta-IEL / Intestinal Epithelial Cell / alphabeta-IEL / CD8alphaalpha IEL / MHC-Deficient Mouse / gammadelta-DETC / Cutaneous GvHR
Research Abstract

Our result shows :
1) The absence of gammadelta-IEL is associated with a reduction in intestinal epithelial cell turnover and a downregulation of the expression of MHC class II molecules.
2) The development of CD8^+ intestinal intraepitehlial T lymphocytes (IEL) was analyzed in mice that are deficient in the expression of MHC class I molecules owing to either a mutanted beta_2M gene or a mutanted TAP-1 gene and in mice doubly lomozygous for beta_2M and TAP-1 mutations. In all mutant mice, the population size of major CD8alphaalpha^+ and CD8alphabeta^+ alphabeta-IEL subsets was drastically reduced. In beta_2M*TCRdelta double mutant mice, however, the CD8alphaalpha^+ but not CD8alphabeta^+alphabeta-IEL subset expanded dramatically. Thus, in the absence of gammadelta-IEL,alphabeta-IEL in beta_2M deficient mice outnumbered those in wild-type littermates. These results indicate that the generation of CD8alphaalpha^+ lymphocyte population of alphabeta- and gammadelta-IEL is not dependent but t … More hat of CD8alphabeta^+ lymphocyte population of alphabeta-IEL is dependent on beta_2M- and/or TAP-1 dependent MHC class I molecules expressed by the controlling cells present in the anatomical site where the development of IEL takes place.
3) After intradermal injection of the autoreactive T cells, delta^<-/-> mice developed significantly enhanced DTH responses and cutaneous GVHD,which persisted longer than those in delta^<+/-> mice. Surprisingly, resistance to the cutaneous GVHD was not induced in the epidermis of delta^<-/-> mice after spontaneous recovery from the GVHD,while the "susceptible" epidermis of delta^<-/-> mice contained large numbers of alphabeta^+ dEC comparable to those in the "resistant" epidermis of delta^<+/-> mice. Injection of day 16 fetal thymocytes from delta^<+/+> mice into delta^<-/-> mice resulted in the appearance of donor-type gammadelta^+ dEC in the epidermis and the reconstitution with the gammadelta^+ dEC restored the protective immune response of the epidermus against the GVHD to nearly normal levels. These results indicate that gammadelta^+ dEC are responsible for the site-restricted protection against cutaneous GVHD. Less

Report

(1 results)
  • 1995 Final Research Report Summary
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] Juan Lafaille: "High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient antimyelin basic protein T cell reseptor transgenic mice." Cell. 78. 399-408 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 南野昌信: "Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice." The Journal of Immunology.153. 2014-2020 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Peter Mombaerts: "Peripheral lymphoid development and function in TCR mutant mice." International Immunology.6. 1061-1070 (1994)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 駒野肇: "Homeostatic regulation of intestinal epithelia by intraepithelial γδ T cells." Proceeding of the National Academy of Sciences USA.92. 6147-6151 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 渡辺守: "Human intestinal epithelial cells produce interleukin 7." Journal of Clinical Investigation.95. 2945-2953 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Pablo Pereira: "Ontogenic development and tissue distribution of Vγl-expressing γ/δ T lymphocytes in normal mice." The Journal of Experimental Medicine.182. 1921-1930 (1995)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 藤浦康良: "Development of CD8αα^+ intestinal intraepithelial T cells in β_2M and/or TAP-1 deficient mice." The Journal of Immunology.(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] 塩原哲夫: "Resistance to cutaneous graft-versus-host disease is not induced in TCR δ gene mutant mice." The Journal of Experimental Medicine.(in press). (1996)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Juan Lafaille: "High incidence of spontaneous autoimmune encephalomyelitis in immunodeficient anti-myelin basic protein T cell reseptor transgenicmice." Cell. 78. 399-408 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Masanobu Nanno: "Development of intestinal intraepithelial T lymphocytes is independent of Peyer's patches and lymph nodes in aly mutant mice." The Journal of Immunology.153. 2014-2020 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Peter Mombaerts: "Peripheral lymphoid development and function in TCR mutant mice." International Immunology.6. 1061-1070 (1994)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Hajime Komano: "Homeostatic regulation of intestinal epithelia by intraepithelial gammadeltaT cells." Proceeding of the National Academy of Sciences USA.92. 6147-6151 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Mamoru Watanabe: "Human intestinal epithelial cells produce interleukin 7." Journal of Clinical Investigation.95. 2945-2953 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Pablo Pereira: "Ontogenic development and tissue distribution of Vgamma1-expressinggamma/deltaT lymphocytes in normal mice." The Journal of Experimental Medicine.182. 1921-1930 (1995)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Yasuyoshi Fujiura: "Development of CD8alphaalpha^+ intestinal intraepithelial T cells in beta_2M and/or TAP-1 deficient mice." The Journal of Immunology.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary
  • [Publications] Tetsuo Shiohara: "Resistance to cutaneous graft-versus-host disease is not induced in TCRdelta gene mutant mice." The Journal of Experimental Medicine.(in press). (1996)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1995 Final Research Report Summary

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Published: 1995-04-01   Modified: 2016-04-21  

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