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

2002 Fiscal Year Final Research Report Summary

• Project/Area Number: 13671238
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General surgery
• Research Institution: The University of Tokushima
• Principal Investigator: KURITA Nobuhiro The University of Tokushima, University Hospital, Assistant, 医学部附属病院, 助手 (30335814)
• Co-Investigator(Kenkyū-buntansha): ITAKURA Mituo The University of Tokushima, Institute for Genome Research, Professor, ゲノム機能研究センター, 教授 (60134227)
• Project Period (FY): 2001 – 2002
• Keywords: NOD mice / Autoimmnity / Islet transplantation / Diabetes / サイクロフォスファミド

Research Abstract

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