title: 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: Department of General Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
authors: Jian
authors: J
authors: Ye
authors: Yu-Ting
authors: YT
authors: Liao
authors: You-Qiang
authors: YQ
authors: Jian
authors: Xiao-Dan
authors: XD
authors: Zhang
authors: Pei
authors: P
authors: Wei
authors: Hui
authors: H
authors: Qi
authors: Chun-Yan
authors: CY
authors: Deng
authors: Fu-Rong
authors: FR
authors: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics; D015551:Autoimmunity / Q000235:genetics / Q000276:immunology*; D002460:Cell Line; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006084:Graft Rejection / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000637:transplantation*; D007515:Islets of Langerhans / Q000378:metabolism / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D058504:Th17 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D014184:Transplantation, Homologous; D000515:alpha 1-Antitrypsin / Q000097:blood / Q000235:genetics / Q000378:metabolism*
chemical_list: D016207:Cytokines; D007328:Insulin; D000515:alpha 1-Antitrypsin