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Molecular mechanism of T cell differentiation

Research Project

Project/Area Number 08044242
Research Category

Grant-in-Aid for international Scientific Research

Allocation TypeSingle-year Grants
SectionJoint Research
Research Field Immunology
Research InstitutionInstitute of Basic Medical Sciences, Univ of Tsukuba

Principal Investigator

NAKAUCHI Hiromitsu  Institute of Basic Medical Sciences, Univ of Tsukuba, 基礎医学系, 教授 (40175485)

Co-Investigator(Kenkyū-buntansha) GACHELINE Ga  Pasteur Institute免疫研究部, 部長
SINGER Alfred  Institute of Basic Medical Sciences, Univ of Tsukuba, 免疫学部門, 部長
SHORTMAN Ken  Institute of Basic Medical Sciences, Univ of Tsukuba, Laboratory
中村 幸夫  筑波大学, 基礎医学系, 講師 (60231479)
TAKAHAMA Yousuke  Institute of Basic Medical Sciences, Univ of Tsukuba, 基礎医学系, 講師 (20183858)
GACHELIN Gabriel  Institute of Basic Medical Sciences, Univ of Tsukuba
MATSUZAKI Yumi  Institute of Basic Medical Sciences, Univ of Tsukuba
GACHELIN Gab  Pasteur Institute, 免疫研究部, 部長
徳元 康人  筑波大学, 基礎医学系, 助手 (70261170)
Project Period (FY) 1996 – 1997
Project Status Completed (Fiscal Year 1997)
Budget Amount *help
¥6,200,000 (Direct Cost: ¥6,200,000)
Fiscal Year 1997: ¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 1996: ¥2,900,000 (Direct Cost: ¥2,900,000)
KeywordsT cell differentiation / lymphoid committed progenitors / MEL-14 / positive selection / granuloma / NKT cells / リンパ球系幹細胞 / Mel-14 / 造血幹細胞 / 胸腺内分化 / 器官培養 / CD4 / CD8 / IL-7受容体
Research Abstract

1) Dr. Shortman's group at WEHI and our group have so far identified the most primitive thymocytes can differentiate into not only T cells, but B,NK as well as dendritic cells. However, presence of the cells with equivalent capacity, namely, lymphoid committed progenitors in bone marrow has been in question. However, we have been able to show that lymphoid committed progenitors are highly enriched in CD34+c-Kit+Sca-1+Lin-Mel-14+fraction of cells in the bone marrow. Dr.Shortman's group is now trying to see if they also differentiate into dendritic cells.
2) In collaboration with Dr. Gachelin of Pasteur Institute, we have found the presence of NKT cells in granuloma formed in response to non-peptidic mycobacterium antigenic challenge. We have also confirmed that granulomas are not formed in Ja28 knock out mice in which NKT cells are lacking. Thus, NKT cells play a primary role in granuloma formatlon.
3) Utilizing a novel fetal thymus organ culture system which was developed in collaboration with Dr. Singer's group at NIH,we have shown the involvement of molecules such as c-kinase, calcineurin, and notch in T cell signaling for positive selection.furthermore, we have developed a highly efficient transduction system to introduce foreign genes into developing thymocytes using retroviral vectors.

Report

(3 results)
  • 1997 Annual Research Report   Final Research Report Summary
  • 1996 Annual Research Report
  • Research Products

    (35 results)

All Other

All Publications (35 results)

  • [Publications] Shoko Sagara,et al.: "B220 expression by T lymphoid progenitor cells in mouse fetal liver." J.lmmunol.158. 666-676 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yumi Matsuzaki,et al.: "Role of bcl-2 in the Development of Lymphoid Cells From the Hematopoietic Stem Cell." Blood.89. 853-862 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshiko Nishimura,et al.: "In vivo analysis of Fas antigen-mediated apoptosis:effects of agonistic anti-mouse Fas mAb of thymus,spleen and liver." Int.lmmunology.9. 307-316 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yousuke Takahama,et al.: "Pertussis toxin can replace T cell receptor signals that induce positive selection of CD8T cells." Eur.J.lmmunol.27. 3318-3331 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Taniguchi,et al.: "Extent of Chimerism Determines the Mode of Tolerance in Mixed Bone Marrow Chimeras." Transplantation Proceeding.29. 1193-1195 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sinya Tamura,et al.: "Expression and function of c-Met,a receptor for hepatocyte growth factor,during thymocyte development." Scand.J.lmmunol.(in press).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] 中村 幸夫・中内 啓光: "アポトーシスと医学" 羊土社, 5 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugawara,T.et al.: "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling." Springer Verlag, Tokyo, 2 (1997)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shoko Sagara, et al.: "B220 expression by T lymphoid progenitor cells in mouse fetal liver." J.Immunol.158. 666-676 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yumi Matsuzaki, et al.: "Role of bcl-2 in the Development of Lymphoid Cells From the Hematopoietic Stem Cell." Blood.89. 853-862 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yoshiko Nishimura, et al.: "In vivo analysis of Fas antigen-mediated apoptosis : effects of agonistic anti-mouse Fas mAb of thymus, spleen and liver." Int.Immunology. 9. 307-316 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Yousuke Takahama, et al.: "Pertussis toxin can replace T cell receptor signals that induce positive selection of CD8T cells." Eur.J.Immunol.27. 3318-3331 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] H.Taniguchi, et al.: "Extent of Chimerism Determines the Mode of Tolerance in Mixed Bone Marrow chimeras." Transplantation Proceedings. 29. 1193-1195 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sinya Tamura, et al: "Expression and function of c-Met, a receptor for hepatocyte growth factor, during thymocyte development." Scand.J.Immunol.(in press).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Sugawara, T.et al.ed.Yakura, H.: Involvement of MAP kinase kinase 1 in T cell receptor signals inducing positive selection of T lymphocytes.In : Kinases and Phosphatases in Lymphocyte and Neuronal Signaling. Springer Verlag, Tokyo, 348-349 (1997)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1997 Final Research Report Summary
  • [Publications] Shoko Sagara, et al.: "B220 expression by T lymphoid progenitor cells in mouse fetal liver." J. Immunol.158. 666-676 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yumi Matsuzaki, et al.: "Role of bcl-2 in the Development of Lymphoid Cells From the Hematopoietic Stem Cell." Blood.89. 853-862 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yoshiko Nishimura, et al.: "In vivo analysis of Fas antigen-mediated apoptosis : effects of agonistic anti-mouse Fas mAb of thymus, spleen and liver." Int. Immunology. 9. 307-316 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Yousuke Takahama, et al.: "Pertussis toxin can replace T cell receptor signals that induce positive selection of CD8 T cells." Eur. J. Immunol.27. 3318-3331 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] H. Taniguchi, et al.: "Extent of Chimerism Determines the Mode of Tolerance in Mixed Bone Marrow Chimeras." Transplantation Proceedings.29. 1193-1195 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sinya Tamura, et al.: "Expression and function of c-Met, a receptor for hepatocyte growth factor, during thymocyte development." Scand. J. Immunol.(in press).

    • Related Report
      1997 Annual Research Report
  • [Publications] 中村 幸夫・中内 啓光: "アポトーシスと医学" 羊土社, 5 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] Sugawara, T. et al.: "Kinases and Phosphatases in Lymphocyte and Neuronal Signaling." Springer Verlag, Tokyo, 2 (1997)

    • Related Report
      1997 Annual Research Report
  • [Publications] M.Nagata: "Apoptosis during an early stage of nephrogenesis induces renal hypoplasia in bd-2 deficient mice." American Journal of Pathology. Vol.148. 1601-1611 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Tsuda: "IL-7 supports D-J but not V-DJ rearrangement of T cell receptor b gene in fetal liver progenitor cells." J.Immunol.Vol.156. 3233-3242 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Tokoro: "CD3-induced apoptosis of CD4+CD8+thymocytes in the absence of clonotypic T-cell antigen receptor." Eur.J.Immunol.Vol.26. 1012-1017 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Osawa: "In vivo self-renewal of c-Kit+Sca+Linlo/-hematopoietic stem cells.INGC04:J.Immunol." Vol.156. 3207-3214 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] H.Taniguchi: "Long-term and multi-lineage bone marrow reconstitution in normal untreated recipient." Transplant,Proc.Vol.28. 1042-1044 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] M.Osawa: "Long-term lymphohematopoietic reconstitution by a single CD34 negative hematopoietic stem cell." Science. Vol.273. 242-245 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Takahama: "Prorbol E ster and Calcium Ionophore can replace TCR signals that induce positive selection of CD4 Tcells." J.Immunol.Vol.157. 1508-1513 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Kawachi: "Characterization of the mouse CD8 beta chain-encoding gene promoter region." Immunogenetics. Vol.44. 358-365 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] S.Sagara: "B220 expression by T lymphoid progenitor cells in mouse fetal liver." J.Immunol.Vol.158. 666-676 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] Y.Matsuzaki: "Role of bcl-2 in the development of lymphoid cells from the hematopoietic stem cell." Blood. (in press).

    • Related Report
      1996 Annual Research Report
  • [Publications] 大澤匡毅: "Annual Review「免疫」1997" 中外医学社, 12 (1996)

    • Related Report
      1996 Annual Research Report
  • [Publications] 高浜洋介: "「<新医科学大系>第8巻 免疫応答-生体の防御機構II」" 中山書店, 9 (1996)

    • Related Report
      1996 Annual Research Report

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Published: 1996-04-01   Modified: 2016-04-21  

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