Alpha-1-antitrypsin for the improvement of autoimmunity and allograft rejection in beta cell transplantation.

Abstract

Islet transplantation offers hope for patients with type 1 diabetes, which is an autoimmune disease. However, islet transplant recipients must overcome two obstacles in both allograft rejection and autoimmune reaction. Alpha-1-antitrypsin (a1-proteinase inhibitor, AAT) possesses anti-inflammatory properties, reduces cytokine-mediated islet damage, and induces specific immune tolerance. In this study, an insulinoma cell line, NIT-1, was transfected with human AAT (hAAT), named NIT-hAAT, and was transplanted to the left renal subcapsular spaces of 7-week-old female non-obese diabetic (NOD) mice (n=22). Cyclophosphamide(CY) was administered to synchronize and accelerate the development of diabetes. Thus, the immunosuppressive and cytoprotective activity of hAAT in β-cell transplantation was investigated. NIT-hAAT has immunomodulatory properties, which delay the onset of autoimmune diabetes, reduce diabetes incidence, inhibit insulitis and β-cell apoptosis, and dampen transplant site inflammation. We propose that NIT-hAAT has a dual function by improving islet autoimmunity and protecting transplanted β-cells from allograft rejection. However, the low expression of hAAT in vivo results in the inability of NIT-hAAT to induce long-term specific immune tolerance and to completely block allograft rejection.

• Authors: Jian Ye, Yu-Ting Liao, You-Qiang Jian, Xiao-Dan Zhang, Pei Wei, Hui Qi, Chun-Yan Deng, Fu-Rong Li
• Journal: Immunology letters (Immunol Lett) Vol. 150 Issue 1-2 Pg. 61-8 (Feb 2013) ISSN: 1879-0542 [Electronic] Netherlands
• PMID: 23333354 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Cytokines
• Insulin
• alpha 1-Antitrypsin

Topics

• Animals
• Apoptosis (genetics)
• Autoimmunity (genetics, immunology)
• Cell Line
• Cytokines (immunology, metabolism)
• Diabetes Mellitus, Type 1 (genetics, immunology, metabolism, therapy)
• Disease Models, Animal
• Female
• Gene Expression
• Graft Rejection (genetics, immunology)
• Humans
• Insulin (metabolism)
• Insulin-Secreting Cells (transplantation)
• Islets of Langerhans (metabolism, pathology)
• Islets of Langerhans Transplantation (adverse effects, immunology)
• Mice
• T-Lymphocytes, Regulatory (immunology)
• Th1 Cells (immunology, metabolism)
• Th17 Cells (immunology)
• Th2 Cells (immunology, metabolism)
• Transplantation, Homologous
• alpha 1-Antitrypsin (blood, genetics, metabolism)