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

NKT细胞在接受抗CD4单克隆抗体处理的小鼠胰岛异种移植物中的作用

基本信息

批准号：
10671145
负责人：
YASUNAMI Yohichi
金额：
$ 2.43万
依托单位：
Fukuoka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 1999
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671145/
关键词：
Islet transplantation NKT cells Rejection Tolerance xenotransplantation Anti-CD4 antibody

项目摘要

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.

胰岛移植是治疗胰岛素依赖型糖尿病的一种潜在方法。然而。针对异体和异种移植胰岛的免疫反应的确切的细胞和分子机制仍然是核的。在本研究中，我们证明了CD4a+VαL4NKT细胞是接受大鼠肝内胰岛移植所必需的，这是最近发现的一种独特的淋巴样细胞谱系。C57BL/6小鼠在移植后给予一定剂量的抗CD4单抗后，可接受大鼠胰岛移植。在这个过程中不需要免疫抑制药物。抗CD4mAb的剂量是关键的，其有益效果似乎与移植后14天左右CD4+NKT细胞的再次出现有关。在Vα14NKT细胞缺陷小鼠中未观察到抗CD4mAb介导的大鼠胰岛异种移植的接受性，Vα14NKT细胞基本上不存在，而常规淋巴样细胞保持完好。此外，将Vα14NKT细胞过继转移到Vα14NKT细胞缺陷小鼠体内，重建了对大鼠胰岛异种移植的接受性。这些结果表明，VCD414NKT细胞在抗α抗体处理的小鼠接受大鼠胰岛异种移植中起着关键作用。