Gene Transfer Technology Group, University College London, 86-96 Chenies Mews, London WC1E 6HXZ, UK.
Institute of Cancer & Genetics, Cardiff University School of Medicine, Heath Park, Cardiff CF14 4XN, UK.
J Immunol Res. 2015;2015:397879. doi: 10.1155/2015/397879. Epub 2015 Jan 31.
Following fetal or neonatal gene transfer in mice and other species immune tolerance of the transgenic protein is frequently observed; however the underlying mechanisms remain largely undefined. In this study fetal and neonatal BALB/c mice received adenovirus vector to deliver human factor IX (hFIX) cDNA. The long-term tolerance of hFIX was robust in the face of immune challenge with hFIX protein and adjuvant but was eliminated by simultaneous administration of anti-CD25+ antibody. Naive irradiated BALB/c mice which had received lymphocytes from donors immunised with hFIX developed anti-hFIX antibodies upon immune challenge. Cotransplantation with CD4+CD25+ cells isolated from neonatally tolerized donors decreased the antibody response. In contrast, cotransplantation with CD4+CD25- cells isolated from the same donors increased the antibody response. These data provide evidence that immune tolerance following perinatal gene transfer is maintained by a CD4+CD25+ regulatory population.
在小鼠和其他物种中进行胎儿或新生儿基因转移后，经常观察到转基因蛋白的免疫耐受；然而，其潜在机制在很大程度上仍未得到阐明。在这项研究中，胎儿和新生儿 BALB/c 小鼠接受腺病毒载体传递人凝血因子 IX（hFIX）cDNA。尽管用 hFIX 蛋白和佐剂进行免疫挑战，但 hFIX 的长期耐受仍然很强，但同时给予抗 CD25+抗体则会消除这种耐受。接受来自用 hFIX 免疫的供体淋巴细胞照射的幼稚 BALB/c 小鼠在受到免疫挑战时会产生抗 hFIX 抗体。从新生儿耐受供体中分离的 CD4+CD25+细胞的共移植降低了抗体反应。相比之下，从同一供体中分离的 CD4+CD25-细胞的共移植增加了抗体反应。这些数据提供了证据，表明围产期基因转移后的免疫耐受是由 CD4+CD25+调节群体维持的。
