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Role of NKT cells in the acceptance of islet xenograftsin mice treated with anti-CD4 monoclonal antibody

Research Project

Project/Area Number 10671145
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field General surgery
Research InstitutionFukuoka University

Principal Investigator

YASUNAMI Yohichi  Fukuoka Univ., Sch. Medicine, Assoc. Prof., 医学部, 助教授 (00166521)

Co-Investigator(Kenkyū-buntansha) 白石 君男  福岡大学, 医学部, 助手 (90187518)
加藤 寿彦  福岡大学, 医学部, 教授 (80078766)
Project Period (FY) 1998 – 1999
Project Status Completed (Fiscal Year 1999)
Budget Amount *help
¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 1999: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1998: ¥2,300,000 (Direct Cost: ¥2,300,000)
KeywordsIslet transplantation / NKT cells / Rejection / Tolerance / xenotransplantation / Anti-CD4 antibody
Research Abstract

Pancreatic islet transplantation represents a potential treatment for insulin-dependent diabetes mellitus. However. the precise cellular and molecular mechanisms of the immune reactions against allogeneic and xenogeneic transplanted islets remain nuclear. In the present study, we demonstrate that CD4a+ Vα l4 NKT cells, a distinct lymphoid cell lineage recently identified, are required for the acceptance of intrahepatic rat islet xenografts. Rat islet xenografts were accepted by C57BL/6 mice when certain doses of anti-CD4mAb were administrated after transplantation. No immunosuppressive drug is required in this procedure. The dose or anti-CD4mAb was critical, and the beneficial effect appeared to be associated with reappearance of CD4 + NKT cells around 14 days after transplantation. The anti-CD4mAb-mediated acceptance of rat islet xenografts was not observed in Vα 14 NKT cell-deficient mice, where essentially no Vα 14 NKT cells exist and conventional lymphoid cells remain intact. Moreover, the adoptive transfer of Vα 14 NKT cells into Vα 14 NKT cell-deficient mice reconstituted acceptance of rat islet xenografts. These results indicate that Vα 14 NKT cells play a crucial role in the acceptance of rat islet xenografts in mice treated with anti-CD4 antibody.

Report

(3 results)
  • 1999 Annual Research Report   Final Research Report Summary
  • 1998 Annual Research Report
  • Research Products

    (8 results)

All Other

All Publications (8 results)

  • [Publications] M. Nakano: "Hepatocyte growth factor is essential for amelioration of hyperghreuie in STZ-induced dia betic mice receiving a margi nel mass of・……"TRANSPLANTATION. 69. 214-221 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y. Ikehara: "CD4+Vα14 NKT cells are essential for the aceep tance of is let xenografts in mice"J clin Iuvest. (印刷中).

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M Nakao, Y Yssunami, T Maki, S Kodama, Y Ikehara, T Nakamura, M Tanaka, S Ikeda: "Hepatocyte growth factor is essential for amelioration of hyperglycemiain streptozotocin-induced diabetic mice receiving a marginal mass of intrahepatic islet grafts."Transplantation. 69(2). 214-221 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] Y Ikehara, Y Yasunami, S Kodama, M Nakano, T Maki, T Nakayama, M Taniguchi, S Ikeda: "CD4 + Va14NKT cells are essential for the acceptance of intrahepaticratislet xenograftsin mice."J Clin Invest. (accepted for publication).

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1999 Final Research Report Summary
  • [Publications] M.Nakano,Y.Yasunami,et al: "Hepatocyte growth factor is essential for amelioration of hyperglycemia in STZ-induced diabetic mice receiving a marginal."TRANSPCANTATION. 69・2. 214-221 (2000)

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Ikehara,Y.Yasunami et al: "CD4+D214NKT cells are essential for the acceptance of intra hepatic islet xenografts is mice"J Clin Invest,accepted for publicalis.

    • Related Report
      1999 Annual Research Report
  • [Publications] Y.Yasunai,et al: "Cellular immune response in the liver of mice rejectiry dutra bepati rat and quniea p.g sid xenoprabts:expansins of intervedatte TCR cell" Transplantatm Proceedings. 32・2. 581 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] T.nagai,Y.Yasunami,et al: "Acceptance of intrabepatic isld alloprobis without immunosupruni in the limited strain asubination of muce from C57BL/6 to BACK" Transplantetium Proceedings. 30・2. 418 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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