Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells
Humoral immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells
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DOI：
10.1182/blood-2002-07-2146
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发表时间：
2003-04-01
期刊：
影响因子：
20.3
通讯作者：
Collen, D
中科院分区：
文献类型：
--
作者：
De Geest, BR;Van Linthout, SA;Collen, D
腺病毒转移人载脂蛋白A-1在Balb/c小鼠诱导强烈的体液免疫反应，对转基因产品时，表达是驱动从无处不在的活性CMV启动子，但不诱导免疫反应时，驱动的肝细胞特异性256碱基对载脂蛋白A-1启动子。在这里，假设进行了测试，这是体液免疫应答循环转基因产品与其在抗原呈递细胞中的表达相关。在腺病毒转移由肝细胞特异性载脂蛋白C-II或1.5-腺苷酸酶（kb）人α（1）-抗胰蛋白酶启动子驱动的人载脂蛋白A-1表达载体后，未观察到体液免疫应答，但在转移由普遍活性U1 b启动子和鼠MHCII Ebeta启动子驱动的载体后诱导了抗体。观察到脾脏中的抗原表达与免疫应答的发生之间存在严格的相关性。共注射1.5 kb人α（1）-抗胰蛋白酶和小鼠MHCII Ebeta启动子驱动的载体导致针对人apo A-1的短暂体液免疫反应，这表明人apo A-1表达的时间过程是人apo A-1耐受性发展的关键决定因素。高滴度的抗体抗人载脂蛋白A-1的抗体用MHCII Ebeta启动子驱动的载体进行皮下基因转移强调了该启动子用于疫苗接种目的的潜力。总之，体液。小鼠中由腺病毒转移诱导的针对循环抗原的免疫应答严格依赖于抗原呈递细胞中的表达。
Adenoviral transfer of human apo A-1 in Balb/c mice induces a strong humoral immune response against the transgene product when expression is driven from the ubiquitously active CMV promoter but induces no immune response when driven by the hepatocyte-specific 256-base pair apo A-1 promoter. Here the hypothesis was tested, which is that the humoral immune response against the circulating transgene product correlates with its expression in antigen-presenting cells. No humoral immune response was observed after adenoviral transfer of vectors with human apo A-1 expression driven by the hepatocyte-specific apo C-II or 1.5-kilobase (kb) human alpha(1)-antitrypsin promoter, but antibodies were induced after transfer with vectors driven by the ubiquitously active U1b promoter and the murine MHCII Ebeta promoter. A strict correlation was observed between antigen expression in the spleen and the occurrence of an immune response. Coinjection of the 1.5-kb human alpha(1)-antitrypsin and the m urine MHCII Ebeta promoter-driven vectors resulted in a very short-lived humoral immune response against human apo A-1, suggesting that the time course of human apo A-1 expression is a critical determinant of the development of tolerance for human apo A-1. High titers of antibodies. against human apo A-1 after. subcutaneous gene transfer with the MHCII Ebeta promoter-driven vector underscore the potential of this promoter for vaccination purposes. In conclusion, humoral. immune response in mice against a circulating antigen induced by adenoviral transfer is strictly dependent on expression in antigen-presenting cells.