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Studies on Immunologic Reconstitution after HLA-haplotype Mismatched parental Marrow Transplantation

Research Project

Project/Area Number 61440043
Research Category

Grant-in-Aid for General Scientific Research (A)

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTOHOKU UNIVERSITY

Principal Investigator

KONNO Tasuke  Research Institute for Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所, 教授 (00004846)

Co-Investigator(Kenkyū-buntansha) MASAYOSHI Minegishi  Research Institute for Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所付属病院, 医員 (20211592)
MASAHIKO Terasawa  Research Institute for Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所, 助手 (80192201)
TETSUO Sato  Research Institute for Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所, 助手 (90170761)
SHIGERU Tsuchiya  Research Institute for Tuberculosis and Cancer, Tohoku University, 抗酸菌病研究所, 助教授 (30124605)
洲崎 健  東北大学, 抗酸菌病研究所附属病院, 助手 (90134048)
Project Period (FY) 1986 – 1987
Project Status Completed (Fiscal Year 1987)
Budget Amount *help
¥25,000,000 (Direct Cost: ¥25,000,000)
Fiscal Year 1987: ¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 1986: ¥21,000,000 (Direct Cost: ¥21,000,000)
KeywordsBone marrow transplantation / HLA-haplotype / histoincompability / I cell-depleted immunodeficiency / flow cytometry / NK activity / NK活性 / 寛容 / HLA / リンパ球膜分化抗原 / 白血病
Research Abstract

A. T cell-depletd, HLA-haplotype mismatched, parental marrow has been usedfor transplant in patients with severe immune deficiency diseases and leukemia. Previously, we succeeded in transplantation of soy bean agglutinin- and sheep red cell rosiesting-fractionated, maternal marrow in apatient with severe combined imunodeficiency (SIDC). Kinetics of immune reconstitution after the bone marrow transplantation (BMT) were investigated in this patient. 1. Cellular immunity recovered relatively rapidly with normal T cell subpopulations and positive delayedtype hyper sensitivity against PPD. Four years later, CD4^+ cells decreased and the ratio of CD4^+/CD8^+ was less than 1.0. Unusual T cells which express CD3 but neither CD4 nor CD8 antigens increased comprising 10 30 % of peripheral T cells. These CD3^+4^-8^SD1 cells, although not identified yet, seemed to correspond to cells which express the <gamma> protein of the T cell receptor but not its <alpha>- and <beta>- chains in association with the CD3 complex. 2. T cells in the patients were shown to be of donor origin but B cells to be of host origin. The reconstitution of humoral immunity was achieved 5 years after BMT, resulting in discontinuation of immunoglobulin replacement. This indicates that HLA haploidentical donor stem cells are able to differentiate and mature to functional T cells which can cooperate with host B cells for antibody production. 3. Little NK actiivty has been demonstrated during the course after BNT in the patient. Leu 7 cells were found soon after engraftment but Leu 11 cells in appeared first 5 years later.
B. Last 2 years, two other patients underwent HLA-mismatched BMT; One with SCID succumbed to severe infection after the treatemnu and the other with Fancom's anemia too early to be evaluated.
C. Five patients with various types of leukemia underwent HLA-mached alogeneic BMT and in all cases, hematologic and immunologic functions have been reconstituted.

Report

(2 results)
  • 1987 Final Research Report Summary
  • 1986 Annual Research Report
  • Research Products

    (17 results)

All Other

All Publications (17 results)

  • [Publications] 今野 多助 他: 日本臨床免疫学会々誌. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegichi,M. etal: Tohoku Journal experimental Medicine. 151. 282-292 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegishs,N.etal: Tohoku Journal experimental Medicine. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegishi,M.etal: Leukemia Research. (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuchiya,S etal: Tohoku Journal experimental Medicine. 150. 455-465 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 今野 多助: Immunohematology-免疫と血液-. 9. 139-143 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Eibl.MM,Rosen FS (editors); Konno,T.: "Primary Immunodeficiency Disease; OMM-1,(MO-1)/LFA-1 deficiency in a Japanese infant with recurrent infection" 378;315-318 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Konno, T et al: "Kinetics of immune recostituti on after HLA-haplotype mismatched bone marrow transplantation: Long-term observation in a patient with severe combined immunodeficiency" Japanese Journal of Clinical Immunology (Japanese). (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegishi, M et al: "Establishment of five human malignant non-T lymphoid cell lines and mixed lymphocyte-tumor reaction" Tohoku Journal of experimental Medicine. 151. 282-292 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegishi, N et al: "Chronic granulomatous disease iwth neutrophilmembrance cytochrome b deficiency: Demonstration by immunohcemical staining with monoclonal anitobdy" Tohoku Journal of experimental Medicine. (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Minegishi, M et al: "Characterization of a precursor T cell line (THP-6) with rearranged T cell receptor chain gene" Leukemia Research. (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Tsuhciya, S et al: "Adaptation of a human monocytic leukemia cell line (THP-1) in a protein-free chemically defined medium" Tohku Journal experimental Medicine. 150. 455-465 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] Eibl MM, Rosen FS (editors); Konno T. et al: Primary Immunodeficiency Disease ; OKM-1 (Mo-1)/LFA-1 deficiency in a Japanese infant with recurrent infection. Excerpta Medica, 315-318 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1987 Final Research Report Summary
  • [Publications] 今野多助 他: 抗酸菌病研究所雑誌. 37. 115-124 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Kitaoka S.et al.: Journal of Medical Virology. 19. 313-323 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Tsuchiya S.et al.: Tohoku Journal of Experimental Medicine. 150. 455-465 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] Eibl MM;Rosen FS(Editors)Konno T.et al.: "Primary Immunodeficiency Diseases(OKM-1(MO-1)/LFA-1 deficiency in a Japanese infant with rucurrent infection)" Excerpta Medica, 378(4) (1986)

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2017-04-05  

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