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

我们制备了NOD- rgp - tgf -β1小鼠，在大鼠胰高血糖素启动子的控制下，pTGF-β1在NOD小鼠胰岛ac细胞中表达。将NOD- rgp - tgf -β1小鼠胰岛移植至自发性糖尿病NOD小鼠。所有NOD- rcp TGF-β1小鼠在自发性糖尿病NOD小鼠移植后10天内均出现排斥反应。在胰岛移植后，在NOD-RGP-TGF-β1小鼠或窝仔体内再注射2次致糖尿病剂量CY （200mg/kg）。结果表明，单次注射CY后，NOD- rgp -TGF-β1小鼠均未发生高血糖，4只NOD- rgp -TGF-β1小鼠中有3只在第二次注射CY后仍保持正常血糖，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并非对效应淋巴细胞的直接保护。而自身反应性T细胞和调节性T细胞的生成减少

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