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2004 Fiscal Year Final Research Report Summary

STRUCTURE OF TCR ON TLYMPHOCYTES HARNESSING GRAFT-VERSUS-LEUKEMIA EFFECT

Research Project

Project/Area Number 14570960
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionAkita University

Principal Investigator

HIROKAWA Makoto  AKITA UNIVERSITY, SCHOOL OF MEDICINE, ASSISTANT PROFESSOR, 医学部, 講師 (50241667)

Co-Investigator(Kenkyū-buntansha) KAWABATA Yoshinari  AKITA UNIVERSITY, SCHOOL OF MEDICINE, LECTURER, 医学部, 助手 (70361227)
SUZUKI Ryuji  SAGAMIHARA NATIONAL HOSPITAL, CLINICAL RESEARCH CENTER, RESEARCH DIRECTOR, 臨床研究センター診断治療研究室, 室長(研究職)
Project Period (FY) 2002 – 2004
KeywordsT cell receptor / Clone / Allogeneic BMT / Leukemia
Research Abstract

We have found that recipients of allogeneic hematopoietic stem cell grafts have a skewing of the αβ TCR repertoire after transplant and this is a result of the proliferation of donor-derived mature T lymphocytes which can survive in recipients for several years. Expansion of the population of donor-derived TCRαβ+ T clones from a cytomegalovirus (CMV)-seropositive bone marrow donor was observed in a CMV-seropositive recipient when developing CMV-associated disease after transplantation. These results suggest that the clonal expansion of TCRαβ+ T cells and resulting skewed αβ TCR repertoire in peripheral blood following allogeneic hematopoietic stem cell transplantation (HSCT) primarily reflect the response to microorganisms. We have also found that stable clonal expansion of Vδ1+ _YδT lymphocytes persisted for several years after human allo-HSCT. CDR3 size spectratyping analysis revealed that twenty-three out of forty-two patients had highly skewed TCR repertoires of the Vδ1+ T cells. There was no apparent association between the oligoclonality of Vδ1+ TCRs and clinical outcome such as GVHD and leukemia relapse. In eight out of seventeen patients examined, the -WGI-amino acid sequence was observed in the CDR3 region of TCRs of clonally expanded Vδ1+ T cells. The -YWG-sequence was observed in four patients. All recipients examined were serologically positive for EBV-VCA IgG and EBNA. Autologous EBV transformed B cells could induce the expansion of Vδ1+ T cells. The CDR3 size distribution patterns of Vδ1+ TCRs became skewed after stimulation with autologous EBV-LCL, and the T cell clone with the -LEEYWGLPH-CDR3 sequence predominated in the culture with autologous EBV-LCL. These results suggest the CDR3 structure may contribute to recognition of EBV-associated antigens by Vδ1+ T cells. Skewing of the Vδ1+ TCR after allo-HSCT may be the result of the response to infectious antigens widely existing in humans such as EBV.

  • Research Products

    (9 results)

All 2004 2003

All Journal Article (9 results)

  • [Journal Article] Contribution of complementarity-determining region 3 of the TCRVδ2 chain to the recognition of aminobisphosphonates by human γδ T cells.2004

    • Author(s)
      Nishimura H, et al.
    • Journal Title

      International Journal of Hematology 79

      Pages: 369-379

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Co-development of dendritic cells along with erythroid differentiation from human CD34^+ cells by tumor necrosis factor-α.2004

    • Author(s)
      Fukaya H, et al.
    • Journal Title

      Experimental Hematology 32

      Pages: 450-460

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gene expression profiling of human erythroid progenitors by micro-serial analysis of gene expression (MicroSAGE)2004

    • Author(s)
      Fujishima N, et al.
    • Journal Title

      International Journal of Hematology 80

      Pages: 239-245

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Monitoring the expression profiles of doxorubicin-resistant K562 human leukemia cells by serial analysis of gene expression.2004

    • Author(s)
      Ichikawa Y, et al.
    • Journal Title

      International Journal of Hematology 79

      Pages: 276-282

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] Gene expression profiling of human erythroid progenitors by micro-serial analysis of gene expression (MicroSAGE).2004

    • Author(s)
      Fujishima N, et al.
    • Journal Title

      International Journal of Hematology 80

      Pages: 239-245

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] The presence and longevity of peripherally expanded donor-derived TCRαβ+mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias2003

    • Author(s)
      Saitoh H, et al.
    • Journal Title

      Leukemia 17

      Pages: 1626-1635

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] T-cell repertoire regeneration after human allogeneic hematopoietic stem cell transplantation : current concept and future direction2003

    • Author(s)
      Hirokawa M, et al.
    • Journal Title

      Recent Research Development in Immunology, Research Signpost, Kerara 5

      Pages: 151-157

    • Description
      「研究成果報告書概要(和文)」より
  • [Journal Article] The presence and longevity of peripherally expanded donor-derived TCRαβ+ mature T lymphocyte clones after allogeneic bone marrow transplantation for adult myeloid leukemias.2003

    • Author(s)
      Saitoh H, et al.
    • Journal Title

      Leukemia 17

      Pages: 1627-1635

    • Description
      「研究成果報告書概要(欧文)」より
  • [Journal Article] T-cell repertoire regeneration after human allogeneic hematopoietic stem cell transplantation : current concept and future direction.2003

    • Author(s)
      Hirokawa M, et al.
    • Journal Title

      Recent Research Development in Immunology(Research Signpost, Kerara) 5

      Pages: 151-157

    • Description
      「研究成果報告書概要(欧文)」より

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Published: 2006-07-11  

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