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Development of Alloreactive T-Cell Depletion for the Prophylaxis of GVHD.

Research Project

Project/Area Number 01570549
Research Category

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

Allocation TypeSingle-year Grants
Research Field Pediatrics
Research InstitutionTokai University School of Medicine

Principal Investigator

KATO Shunichi  Tokai University School of Medicine Department of Pediatrics Associate Professor, 医学部, 助教授 (70096212)

Co-Investigator(Kenkyū-buntansha) YABE Hiromasa  same as above, Instructor, 医学部, 助手 (70220217)
YABE Miharu  same as above, Assistant Professor, 医学部, 講師 (40172514)
Project Period (FY) 1989 – 1990
Project Status Completed (Fiscal Year 1990)
Budget Amount *help
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1990: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1989: ¥1,000,000 (Direct Cost: ¥1,000,000)
KeywordsAllogeneic BMT / GVHD / Alloreactive T-cell / Galactose Oxidase / アロ反応性T細胞除去 / GVHD予防 / 特異的Tリンパ球除去 / リンパ球混合培養
Research Abstract

In this study we attempted to develop a method which will selectively deplete a particular population of T cells that recognizes surfece alloantigen of recipient cells. Galactose oxidase was labeled onto the surface of mitomycin-C (MMC) treated splenic lymphocytes from BALB/C mice (H-2^d, Mls^b). Mouse splenic lymphocytes from DBA/2 (H-2^d, Mls^a) mixed with the galactose oxidase labelled BALB/C lymphocytes allowed to DBA/2 cells which recognized the Mls^b on the BALB/C cells to make direct contact with the galactose oxidase labeled BALB/C cells. By adding galactose, sodium iodide and catalase to the mixture, the contacting stimulator cells which generate hydrogen peroxide in the vicinity of the contacting responder cells and the iodine ions will exert a toxic effect on the responder cells while non-specific toxicity was prevented by catalase. When fresh MMC-treated BALB/C lymphocytes were added to the cell mixture, the mixed lymphocyte cell reaction against BALB/C cells by the treated DBA/2 lymphocytes was abolished. On the other hand, when fresh MMC-treated lymphocytes from C57BL/6 mice (H-2^b, Mls^b) were mixed with the treated DBA/2 cells, the mixed lymphocyte response against C57BL/6 cells by the treated DBA/2 lymphocytes was partially retained. Therefore, although some non-specific toxicity was present, a method to deplete specific T-lymphocyte which recognize major histcompatibility antigen from a mixed cell population while maintaining immune responsiveness towards other antigens was developed. Application of this method to human immune system resulted in failure because of greater stability of human lymphocyte to hydrogen peroxide. This method may have a beneficial effect on the control of post transplant immunity and may be used as a prophylaxis of graft-versus-host disease with some modification.

Report

(3 results)
  • 1990 Annual Research Report   Final Research Report Summary
  • 1989 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Yabe H.,Watanabe T,et al: "A trial of alloreactive Tーcell depletion using biotinyーlated galactose oxidase for the prevention of acute graftーversusーhost disease." Tokai J Exp Clin Med. 13. 227-238 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 矢部 普正・加藤 俊一: "T細胞除去骨髄移植の問題点" 臨床免疫. 21. 1142-1148 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 矢部 普正・加藤 俊一: "GVHD対策の最近の進歩" 今日の移植. 4. 33-39 (1991)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yabe H. Watanabe T, Kimura M, et al: "A trial of alloreactive T-cell depletion using biotinylated galactose oxidase for the prevention of acute graft-versus-host disease." Tokai J Exp Clin Med. 13(4, 5). 227-238 (1988)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yabe H, Kato S: "Problems in T-cell depleted allogeneic bone marrow transplantation." Clinical Immunology. 21(7). 1142-1148 (1989)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] Yabe H, Kato S: "Recent progress in treatment for graft-versus-host disease." Transplantation Now. 4(1). 33-39 (1991)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1990 Final Research Report Summary
  • [Publications] 矢部 普正・加藤 俊一: "T細胞除去骨髄移植の問題点" 臨床免疫. 21. 1142-1148 (1989)

    • Related Report
      1990 Annual Research Report
  • [Publications] 矢部 普正・加藤 俊一: "GVHD対策の最近の進歩" 今日の移植. 4. 33-39 (1991)

    • Related Report
      1990 Annual Research Report
  • [Publications] Hiromasa Yabe et al: "A Trial of alloreactive T-cell depletion using biotinylated galactoseoxidase for the prevention of acute graff-versus-host disease" Tokai J Exp Clin Med. 13. 227-238 (1988)

    • Related Report
      1989 Annual Research Report

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Published: 1989-04-01   Modified: 2016-04-21  

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