The induction of the immunotolerance in islet transplantation model using transgenic NOD mice in which TGF-β1 is expressed in pancreatic α cell

胰腺α细胞表达TGF-β1转基因NOD小鼠诱导胰岛移植模型免疫耐受

• 批准号: 13671238
• 负责人: KURITA Nobuhiro
• 金额: $ 2.11万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671238/
• 关键词: NOD mice; Autoimmnity; Islet transplantation; Diabetes; サイクロフォスファミド; サイクロフォスファシド; TGF-β1; I型糖尿病

We produced NOD-RGP-TGF-β1 mice in which pTGF-β1 is expressed in islet ac cells of NOD mice under the control of the rat glucagon promoter. Islets of NOD-RGP-TGF-β1 mice were transplanted to spontaneously diabetic NOD mice. The all grafts of NOD-RCP TGF-β1 mice in spontaneously diabetic NOD mice was rejected within 10 days post-transplantation. The diabetogenic dose of CY (200mg/kg) was additionally injected two times to NOD-RGP-TGF-β1 mice or littermates after islet transplantation. All littermates were induced hyperglycemia by single injection of CY. However, none of NOD-RGP-TGF-β1 mice were induced hyperglycemia by single injection of CY and three out of four NOD-RGP-TGF-β1 mice remained normoglycemia by second injection of CY. As a result, the protection mechanism against autoimmune diabetes in NOD mice by local paracrine TGF-β1 is not direct protction against effector lymphocytes, but decrease of generation of autoreactive T cells and the generation of regulatory T cells

我们制备了NOD-RGP-TGF-β1小鼠，其中pTGF-β1在大鼠胰高血糖素启动子的控制下在NOD小鼠的胰岛ac细胞中表达。将NOD-RGP-TGF-β1小鼠的胰岛移植到自发性糖尿病NOD小鼠。NOD-RCP TGF-β1小鼠在自发性糖尿病NOD小鼠中的所有移植物在移植后10天内被排斥。NOD-RGP-TGF-β1小鼠或胰岛移植后的同窝小鼠，分别注射致糖尿病剂量CY（200 mg/kg）2次。所有同窝仔均通过单次注射CY诱导高血糖。而NOD-RGP-TGF-β1小鼠单次注射CY后均未出现高血糖，第二次注射CY后4只NOD-RGP-TGF-β1小鼠中有3只血糖正常。因此，局部旁分泌TGF-β1对NOD小鼠自身免疫性糖尿病的保护机制不是直接保护效应淋巴细胞，而是减少自身反应性T细胞和调节性T细胞的产生