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1999 Fiscal Year Final Research Report Summary

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
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.

  • Research Products

    (4 results)

All Other

All Publications (4 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
  • [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
  • [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
  • [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

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Published: 2001-10-23  

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