Department of General Surgery, The Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, China.
Immunol Lett. 2013 Feb;150(1-2):61-8. doi: 10.1016/j.imlet.2013.01.009. Epub 2013 Jan 16.
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.
胰岛移植为 1 型糖尿病患者（一种自身免疫性疾病）带来了希望。然而，胰岛移植受者必须克服同种异体排斥和自身免疫反应这两个障碍。α-1-抗胰蛋白酶（a1-蛋白酶抑制剂，AAT）具有抗炎特性，可减少细胞因子介导的胰岛损伤，并诱导特异性免疫耐受。在这项研究中，将人 AAT（hAAT）转染到胰岛素瘤细胞系 NIT-1 中，命名为 NIT-hAAT，并将其移植到 7 周龄雌性非肥胖型糖尿病（NOD）小鼠（n=22）的左肾被膜下腔。环磷酰胺（CY）用于同步和加速糖尿病的发展。因此，研究了 hAAT 在β细胞移植中的免疫抑制和细胞保护作用。NIT-hAAT 具有免疫调节特性，可延迟自身免疫性糖尿病的发病，降低糖尿病发病率，抑制胰岛炎和β细胞凋亡，并抑制移植部位炎症。我们提出，NIT-hAAT 通过改善胰岛自身免疫和保护移植的β细胞免受同种异体排斥具有双重功能。然而，hAAT 在体内的低表达导致 NIT-hAAT 无法诱导长期特异性免疫耐受并完全阻断同种异体排斥。
