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Mechanisms for differentiation and selection of T, NKT and NK cells

Research Project

Project/Area Number 11694241
Research Category

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

Allocation TypeSingle-year Grants
Section一般
Research Field Immunology
Research InstitutionInstitute of Basic Medical Sciences, University of Tsukuba

Principal Investigator

NAKAUCHI Hiromistu  Inst.of Basic Med.Sci., Univ of Tsukuba, Professor, 基礎医学系, 教授 (40175485)

Co-Investigator(Kenkyū-buntansha) TAKAHAMA Yosuke  Inst.of Genome Research., Univ of Tokushima, Professor, ゲノム機能研究センター, 教授 (20183858)
SHIBUYA Kazuko  Inst.of Clinical Med.Sci., Univ of Tsukuba, Lecturer, 臨床医学系, 講師 (00302406)
SHIBUYA Akira  Inst.of Basic Med.Sci., Univ of Tsukuba, Associate Professor, 基礎医学系, 助教授 (80216027)
TAHARA Satoko  JSTS,Research fellow, 特別研究員
Project Period (FY) 1999 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 2000: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1999: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsNK cells / granuloma / inhibitory receptor / LFA-1 / DNAM-1 / adhesion molecule / Fc receptor / NKT cells / Fc受容体 / 肉芽腫 / Mycobacterium
Research Abstract

1) In collaboration with Dr.Gabriel Gahchelin of Pasteur Institute in Paris, France, we identified the role of NKT cells in granuroma formation induced by mycobacterium. NKT cells play a key role in the intial phase of granuloma formation. J α 281 gene knockout mice which lack NKT cells showed significantly reduced granuloma formation.
2) In collaboration with Dr.Lewis Lanier of University of San Francisco, we clarified the role of DNAM-1 in the signal transduction from LFA-1. Stimulation of T cell receptor gives LFA-1 an inside-out signal that in turn increases the ligand binding affinity and an association of LFA-1 with DNAM-1. Upon interaction with ligands, LFA-1 associates with a src family tyrosine kinase Fyn which phosphorylates DNAM-1 to transduce signals in side the cell.
3) A gene encoding a Fc receptor for lgM and lgA was isolated. We not only characterized its structure and expression, but also clarified its role in early phase of immunological defense system against microbes.
4) In order to stufdy the role of Notch signals in T cell development, Hes-1 gene was introduced into immature T cells using a retroviral vector. Transduced cells were cultured using fetal thymus organ culture system. Forced expression of Hes-1 increased cell growth but did not alter the proportion of CD4/CD8 T cell. Molecules other than Hes-1in the Notch signaling system seem to be responsible for CD4/CD8 commitment of T lymphoid cells.
5) A novel receptor specfically expressed in NK cells and macrophages has been isolated. This receptor with an Ig-like domain may serve as an inhibitory type receptor for NK cells.

Report

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

    (42 results)

All Other

All Publications (42 results)

  • [Publications] Sakamoto N., et al.: "A novel Fc receptor for IgA and IgM is expressed on hematopoietic and non-hematopoietic tissues."Eur.J.Immunol.,. (in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuya, A., et al.: "Fcα/μ receptor mediates endocytosis of IgM-coated microbes."Nature Immunol.. 1. 441-446 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hsu HC, et al.: "Hematopoietic stem cells express Tie-2 receptor in the murine fetal liver."Blood. 96. 3757-3762 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sudo K, et al.: "Age-associated characteristics of murine hematopoietic stem cells."J Exp Med. 192. 1273-1280 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ema H, et al.: "Ir Vitro Self-Renewal Division of Hematopoietic Stem Cells."J Exp Med. 192. 1281-1288 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hideo Ema and Hiromitsu Nakauchi.: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo."Blood. 95. 2284-2288 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneda M, et al.: "A role for pref-1 and HES-1 in thymocyte development."J Immunol. 164. 256-264 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiki Y, et al.: "Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone fragments."Exp Hematol . 28. 792-801 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyama T, et al.: "Molecular cloning and characterization of CRLM-2, a novel type 1 cytokine receptor preferentially expressed in hematopoietic cells."Biochem Biophys Res Commun. 272. 224-229 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsujiro Osawa, et al.: "Characterization of Murine Interleukin-13 Receptor alpha 1 Gene."Immunogenetics.. 51. 974-981 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I.Apostolou, et al.: "Murine natural killer cells contribute to the granulomatous reaction caused by mycobacterial cell walls."Proc Natl Acad Sci USA. 96. 5141-5146 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuko Shibuya, et al.: "Physical and Functional Association of LFA-1 with DNAM-1 Adhesion Molecule."Immunity. 11. 615-623 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakauchi H, et al.: "Hematopoietic.Stem Cells"Ann N Y Acad Sci. 291 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakauchi H, et al.: "Cell Therapy."Springer-Verlag Tokyo.. 240 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuya A., et al.: "Leukocyte Typing VII"Oxford Univ.Press(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sakamoto N.et al: "A novel Fc receptor for lgA and lgM is expressed on hematopoietic and non-hematopoietic tissues"Eur.J.Immunol. (in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuya, A., et al.: "Fca/m receptor mediates endocytosis of IgM-coated microbes"Nature Immunol. 1. 441-446 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hsu HC.et al.: "Hematopoietic stem cells express Tie-2 receptor in the murine tetal liver"Blood. 96. 3757-3762 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sudo K.et al.: "Age-associated characteristics of murine hematopoietic stem cells"J Exp Med. 192. 1273-1280 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ema H,et al.: "In Vitro Self-Renewal Division of Hematopoietic Stem Cells"J Exp Med. 192. 1281-1288 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hideo Ema and Hiromitsu Nakauchi: "Expanshion of hematopoietic stem cells in the developing liver of a mouse embryo"Blood. 95. 2284-2288 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kaneta M.et al: "A role for pret-1 and HES-1 in trymocyte development."J Immunol. 164. 256-264 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujiki Y,et al.: "Dominant expansion of human T cells in non-obese diabetic/severe combined immunodeficiency mice implanted with human bone tragments"Exp Hematol. 28. 792-801 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Hiroyama T,et al.: "Molecular cloning and characterization of CRLM-2, a novel type 1 cytokine receptor preferentially expressed in hematopoietic cells"Biochem Biophys Res Commun. 272. 224-229 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Mitsujiro Osawa, et al.: "Characterzation of Munne Interleukin-13 Receptor alpha 1 Gene."Immunogenetics. 51. 974-981 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] I.Apostolou, et al.: "Murine natural killer cells contribute to the granulomatous reaction caused by mycobacterial cell wallls."Proc Nati Acad Sci USA. 96. 5141-5146 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kazuko Shibuya, et al.: "Physical and Functinal Association of LFA-1 with DNAM-1 Adhesion Molecule."Immunity. 11. 615-623 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakauchi H.et al.: "Further charactenzation of CD34-low/negative mouse hematoppietic stem cells"Ann NY Acad Sci 872 : 57-66 ; discussion. 66-70 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Nakauchi H,et al.: "Isolation and Characterzation of CD34-Low/Negative Mouse Hematopoietic Stem cells"In : Cell Therapy Y.Ikeda, J.Hata, S.Koyasu, Y.Kawakami, Y.Hattori(eds).Springer-Verlao Tokyo. 95-103 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuya A., et al.: "Leukocyte Typing VII"Oxford Univ.Press(in Press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Shibuya K.et al.: "Physical and functional association of LFA-1 with DNAM-1 adhesion molecule."Immunity. 11巻. 615-623 (1999)

    • Related Report
      2000 Annual Research Report
  • [Publications] Lanier L.L.et al.: "DNAM-1, PTA1, TLisa (CD226)."Protein Reviews On The Web. 1巻. 68-71 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibuya A.et al.: "Fcα/μ receptor mediates endocytosis of IgM-coated microbes."Nature Immunol.. 1巻. 441-446 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Sakamoto N.et al.: "A novel Fc receptor for IgA and IgM is expressed on hematopoietic and non-hematopoietic tissues."Eur.J.Ommunol. (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] Shibuya A.et al.: "Leukocyte Typing VII"Oxford University Press (in press).

    • Related Report
      2000 Annual Research Report
  • [Publications] I..Apostolou,et al.: "Murine natural killer cells contribute to the granulomatous reaction caused by mycobacterial cell walls."Proc Natl Acad Sci USA. 96. 5141-5146 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ken-ichi Matsuda,et al.: "A Novel Stromal Cell-Dependent B Lymphoid Stem-Like Cell Line That Induces Immunoglobulin Gene Rearrangement."J.Biochem.. 125. 602-612 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Tomoyuki Yamaguchi,et al.: "Human Immunodeficiency Virus Type 1 Vpr Modifies Cell Proliferation via Multiple Pathways."Microbiol.Immunol.. 43. 437-447 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hideyuki Murata,et al.: "Microchimerism in Japanese women patients with systemic sclerosis."The Lancet.. 354. 220 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] DONG Ku Kim^*,YUTAKA FUJIKI^*, et al: "Comparison of Hematopoietic Activities of Human Bone Marrow and Umbilical Cord Blood CD34 Positive and Negative Cells."STEM CELLS. 17. 286-294 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Kazuko Shibuya,et al.: "Physical and Functional Association of LFA-1 with DNAM-1 Adhesion Molecule."Immunity. 11. 615-623 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Hiromitsu Nakauchi.: "The Hematopoietic Stem Cell.edited by Shirkis,Orlic and Kantz."Academic Press. 14 (1999)

    • Related Report
      1999 Annual Research Report

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Published: 1999-04-01   Modified: 2016-04-21  

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