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Factors determining T lineage commitment in haematopoietic stem cell.

Research Project

Project/Area Number 16390045
Research Category

Grant-in-Aid for Scientific Research (B)

Allocation TypeSingle-year Grants
Section一般
Research Field General anatomy (including Histology/Embryology)
Research InstitutionTohoku University

Principal Investigator

ITOH Tsunetoshi  Tohoku University, Graduate School of Medicine, Professor, 大学院・医学系研究科, 教授 (90004746)

Co-Investigator(Kenkyū-buntansha) MATSUTANI Takaji  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (70372290)
OGATA Masaki  Tohoku University, Graduate School of Medicine, Research Associate, 大学院・医学系研究科, 助手 (50311907)
SUZUKI Ryuji  National Sagamihara Hospital, Clinical Research Center For Allergy & Rheumatology, Research Head, 臨床研究センター, 室長 (70373470)
曽我 浩之  東北大学, 大学院・医学系研究科, 助手 (20282121)
Project Period (FY) 2004 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥14,900,000 (Direct Cost: ¥14,900,000)
Fiscal Year 2005: ¥6,800,000 (Direct Cost: ¥6,800,000)
Fiscal Year 2004: ¥8,100,000 (Direct Cost: ¥8,100,000)
KeywordsThymus / Hematopoietic stem cells / Lineage commitment / Microenvironment / Cytokine / T lymphocyte
Research Abstract

T lymphocytes differentiate and mature in the thymus. It has been still controversial whether multi-potent haematopoietic stem cells (HSCs) enter the thymus or progenitors committed to T cell lineage do. It remains also unknown how HSCs are committed to T cell lineage, how a small number of T cells are selected or how mature T cell receptor (TCR) repertoire is formed. Using electron micrographic and immunohistochemical studies, we attempted to isolate HSCs in the thymus of CTS mice (sister strain to NOD, defect in emigration of mature T cells from the thymus to periphery). By using molecular biological technique, we studied thymocyte development and thymic selection in different strains of mice. Novel findings were revealed through these studies.
1. We took more than ten thousand electron micrographs and frequently found neutrophils and eosinophils at the stage of development from the myelocyte to the metamyelocyte in the thymic parenchyma. We also isolated erythroids (reticulocytes, er … More ythrocytes) and megakaryocytes. This is the first report to demonstrate that presence of megakaryocytes in thymus, suggesting multi-lineage HSCs enter into the thymus. Cytokine production supporting hematopoiesis in the thymus was confirmed with RT-PCR. Collectively, these results suggest that multi-lineage HSCs immigrate into the thymus.
2. TCR repertoire is largely different among different strains of mice in mature thymocytes but not in immature thymocytes at earlier stages. This suggests that pre-selection TCR repertoire is determined by some genetic factors conserved among mouse strains.
3. We demonstrated that CDR3 length shortening was occurred in both CD4SP and CD8SP. The extent of CDR3 shortening was remarkable in CD4SP than in CD8SP and varied among different strains of mice, suggesting that the CDR3 shortening was influenced by MHC haplotype. The CDR3 shortening was dependent on V segment. We assumed that structural feature of Vbeta segment encoded in germline impacts on CDR3 length. Less

Report

(3 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • Research Products

    (24 results)

All 2006 2005 2004

All Journal Article (24 results)

  • [Journal Article] Limited VH gene usage in B-cell clones established with nurse-like cells from patients with rheumatoid arthritis2006

    • Author(s)
      Shino Nakamura-Kikuoka
    • Journal Title

      Rheumatology (Oxford) 45・5

      Pages: 549-557

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alteration of T cell receptor repertoires during thymic development2006

    • Author(s)
      Takaji Matsutani
    • Journal Title

      Scandinavian Journal of Immunology (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 胸腺選択によるT細胞受容体レパトアとCDR3長の変化2006

    • Author(s)
      松谷 隆治
    • Journal Title

      リンパ学 (印刷中)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Limited VH gene usage in B-cell clones established with nurse-like cells from patients with rheumatoid arthritis2006

    • Author(s)
      Shino Nakamura-Kikioka
    • Journal Title

      Rheumatology (Oxford) 45-5

      Pages: 549-557

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alteration of T cell receptor repertoires during thymic development2006

    • Author(s)
      Takaji Matsutani
    • Journal Title

      Scandinavial Journal of Immunology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Alterations of T cell receptor repertoire and CDR3 length2006

    • Author(s)
      Takaji Matsutani
    • Journal Title

      Japanese Journal of Lymphology (in press)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Limited VH gene usage in B-cell clones established with nurse-like cells from patients with rheumatoid arthritis2006

    • Author(s)
      Shino Nakamura-Kikuoka S
    • Journal Title

      Rheumatology (Oxford) (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] 胸腺選択によるT細胞受容体レパトアとCDR3長の変化2006

    • Author(s)
      松谷 隆治
    • Journal Title

      リンパ学 (In press)

    • Related Report
      2005 Annual Research Report
  • [Journal Article] WBN/Kob-Ht Rats Spontaneously Develop Dermatitis under Conventional Conditions : Another Possible Model for Atopic Dermatitis2005

    • Author(s)
      Makoto Asakawa
    • Journal Title

      Experimental Animals 54・5

      Pages: 461-465

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor2005

    • Author(s)
      Ken-ichi Yamazaki
    • Journal Title

      European Journal of Immunology 35・4

      Pages: 1211-1219

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunosuppression by Morphine-Induced Lymphocyte Apoptosis : Is It a Real Issue?2005

    • Author(s)
      Takeshi Ohara
    • Journal Title

      Anesthesia and Analgesia 101・4

      Pages: 1117-1122

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] WBN/Kob-Ht Rats Spontaneously Develop Dermatitis under Conventional Conditions : Another Possible Model for Atopic Dermatitis2005

    • Author(s)
      Makoto Asakawa
    • Journal Title

      Experimental Animals 54-5

      Pages: 461-465

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptors2005

    • Author(s)
      Ken-ichi Yamazaki
    • Journal Title

      European Journal of Immunology 35-4

      Pages: 1211-1219

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunosuppression by Morphine-Induced Lymphocyte Apoptosis : Is It a Real Issue?2005

    • Author(s)
      Takeshi Ohara
    • Journal Title

      Anesthesia and Analgesia 101-4

      Pages: 1117-1122

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Immunosuppression by Morphine-Induced Lymphocyte Apoptosis : Is It a Real Issue?2005

    • Author(s)
      Takashi Ohara
    • Journal Title

      Anesthesia and Analgesia 101・4

      Pages: 1117-1122

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Accumulation of Intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor2005

    • Author(s)
      Ken-ichi Yamazaki
    • Journal Title

      European Journal of Immunology 35・4

      Pages: 1211-1219

    • Related Report
      2005 Annual Research Report
  • [Journal Article] WBN/Kob-Ht Rats Spontaneously Develop Dermatitis under Convemtional Conditions : Another Possible Model for Atopic Dermatitis2005

    • Author(s)
      Makoto Asakawa M
    • Journal Title

      Experimental Animals 54・5

      Pages: 461-465

    • Related Report
      2005 Annual Research Report
  • [Journal Article] Accumulation of intestinal intraepithelial lymphocytes in association with lack of polymeric immunoglobulin receptor.2005

    • Author(s)
      Yamazaki, K., Shimada, S., Kato-Nagoka, N., Soga, H., Itoh, T., Nanno, M.
    • Journal Title

      Eur.J.Immunol. (In press)

    • Related Report
      2004 Annual Research Report
  • [Journal Article] DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes2004

    • Author(s)
      Kei Yaguchi
    • Journal Title

      Cell Tissue Research 315・1

      Pages: 71-84

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper 1/T cytotoxic 1 type cytokines in gastric and colorectal tumors.2004

    • Author(s)
      Takaji Matsutani
    • Journal Title

      International Journal of Oncology 25・1

      Pages: 133-141

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes2004

    • Author(s)
      Kei Yaguchi
    • Journal Title

      Cell Tissue Research 315-1

      Pages: 71-84

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper 1/T cytotoxic 1 type cytokines in gastric and colorectal tumors2004

    • Author(s)
      Takaji Matsutani
    • Journal Title

      Internationall Journal of Oncology 25-1

      Pages: 133-141

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] DNA fragmentation and detachment of enterocytes induced by anti-CD3 mAb-activated intraepithelial lymphocytes.2004

    • Author(s)
      Yaguchi, K., Kayaba, S., Soga, H., Yamagishi, M., Tamura, A., Kasahara, S., Itoh, T.
    • Journal Title

      Cells Tissue Res. 315

      Pages: 71-84

    • Related Report
      2004 Annual Research Report
  • [Journal Article] Evidence for existence of oligoclonal tumor-infiltrating lymphocytes and predominant production of T helper1/cytotoxic 1 type cytokines in gastric and colorectal tumors.2004

    • Author(s)
      Matsutani, T., Shiiba, K., Yoshioka, T., Tsuruta, Y., Suzuki, R., Ochi, T., Itoh, T., Musha, H., Mizoi, T., Sasaki, I.
    • Journal Title

      Int.J.Oncol. 25

      Pages: 133-141

    • Related Report
      2004 Annual Research Report

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Published: 2004-04-01   Modified: 2016-04-21  

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