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Role of NKT cells in acceptance of pancreatic islet allografts in mice.

NKT 细胞在小鼠胰岛同种异体移植物接受中的作用。

基本信息

批准号：
12671189
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：
2000
资助国家：
日本
起止时间：
2000 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671189/
关键词：
islet transplantation NKT cells rejection tolerance allotransplantation donor specific transfusion

项目摘要

Pancreatic islet transplantation represents a potential treatment for insulir dependent diabetes mellitus. However, the precise cellular and moleculai mechanisms of immune reactions against allogeneic islets remain uncleatfn the present study, we determined whether NKT cells, which have been recently identified as a distinct lymphoid cell lineage, play a role in acceptance of isl allografts in mice treated with donor specific transfusion (DST). For those purposes, Vα14 NKT cell knockout mice are used asNKT cell deficient recipients.Pancreatic islet transplantation represents a potential treatment for insulir dependent diabetes mellitus. However, the precise cellular and moleculai mechanisms of immune reactions against allogeneic islets remain uncleatfn the present study, we determined whether NKT cells, which have been recently identified as a distinct lymphoid cell lineage, play a role in acceptance of isl allografts in mice treated with donor specific transfusion (DST). For those purposes, Vα14 NKT cell knockout mice are used asNKT cell deficient recipients.BALB/c islet allografts were accepted in streptozotocin-induced diabeti C57BL/6 mice (wild-type) by DST in conjunction with CTLA4-Ig. In marked contrast, all BALB/c islet allgrafts were rejected with the similar treatment whe NKT cell-deficient mice are used as recipients, indicating that NKT cells an required for the acceptance of islet allografts by DST The molecule(s) of NKT cells associated with the acceptance is currently under investigation by the analysis of real-time PCR on FiCS-sorted NKT cells.A novel procedure to prevent allograft rejection by means of CTLA4Ig was also investigated.

胰岛移植是治疗胰岛素依赖型糖尿病的一种有效方法。然而，针对同种异体胰岛的免疫反应的精确的细胞和分子机制仍不清楚。在本研究中，我们确定了最近被鉴定为独特的淋巴样细胞谱系的NKT细胞是否在用供体特异性输血（DST）处理的小鼠中的胰岛同种异体移植物的接受中起作用。为此，我们采用Vα14 NKT细胞敲除小鼠作为NKT细胞缺陷型受体，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，针对同种异体胰岛的免疫反应的精确的细胞和分子机制仍不清楚。在本研究中，我们确定了最近被鉴定为独特的淋巴样细胞谱系的NKT细胞是否在用供体特异性输血（DST）处理的小鼠中的胰岛同种异体移植物的接受中起作用。以Vα14 NKT细胞敲除小鼠作为NKT细胞缺陷型受体，通过DST联合CTLA 4-IG，将BALB/c胰岛移植于链脲佐菌素诱导的C57 BL/6小鼠（野生型）。与此形成鲜明对比的是，所有的BALB/c胰岛移植物在类似的处理下都被排斥，当NKT细胞缺陷小鼠用作受体时，表明NKT细胞是DST接受胰岛同种异体移植物所必需的。目前正在通过FiCS上的实时PCR分析来研究与接受相关的NKT细胞的分子。本研究还探讨了一种通过CTLA 4 Ig预防同种异体移植排斥反应的新方法。