Chan C C, Li Y, Sun B, Li Q, Matteson D M, Shen D F, Nussenblatt R B, Zhai Y
Laboratory of Immunology, National Eye Institute, National Institutes of Health, Bethesda, MD 20892-1858, USA.
J Autoimmun. 1998 Apr;11(2):111-8. doi: 10.1006/jaut.1997.0187.
Experimental melanin-protein induced uveitis (EMIU) is a T-cell mediated autoimmune uveitis induced by immunization with bovine uveal melanin protein. Gp100, a melanocyte lineage-specific protein, is identified as a human melanoma antigen. A recombinant adenovirus construct encoding gp100 (Ad2CMV-gp100) has been used as a vaccine for cancer therapy. This study examines the effect of Ad2CMV-gp100 on EMIU. To induce EMIU, rats were injected intraperitoneally on day 7 before immunization with ad2CMV-gp100, control adenovirus encoding LacZ (Ad2CMV-LacZ), or no virus. On day 21 after immunization, the right eye was processed for histology and the left eye was analysed for cytokines by quantitative reverse transcriptase-polymerase chain reaction. Western blot analysis showed that uveal melanin-protein contains gp100. In three independent experiments, ocular inflammation was significantly suppressed, and expression of ocular IL-12p40 mRNA was much lower in the rats which received Ad2CMV-gp100 before immunization than in those that received Ad2CMV-LacZ or no virus. No abnormalities developed in rats which received Ad2CMV-gp100 or Ad2CMV-LacZ alone. Therefore, Ad2CMV-gp100 injection prevents the development of EMIU, at least in part, through cytokine regulation.
实验性黑色素 - 蛋白诱导性葡萄膜炎（EMIU）是一种由牛葡萄膜黑色素蛋白免疫诱导的T细胞介导的自身免疫性葡萄膜炎。Gp100是一种黑色素细胞谱系特异性蛋白，被鉴定为人类黑色素瘤抗原。一种编码Gp100的重组腺病毒构建体（Ad2CMV - Gp100）已被用作癌症治疗的疫苗。本研究考察了Ad2CMV - Gp100对EMIU的影响。为诱导EMIU，在免疫前第7天给大鼠腹腔注射Ad2CMV - Gp100、编码LacZ的对照腺病毒（Ad2CMV - LacZ）或不注射病毒。免疫后第21天，对右眼进行组织学处理，对左眼通过定量逆转录 - 聚合酶链反应分析细胞因子。蛋白质印迹分析表明葡萄膜黑色素蛋白含有Gp100。在三个独立实验中，眼部炎症得到显著抑制，免疫前接受Ad2CMV - Gp100的大鼠眼部IL - 12p40 mRNA的表达远低于接受Ad2CMV - LacZ或未注射病毒的大鼠。单独接受Ad2CMV - Gp100或Ad2CMV - LacZ的大鼠未出现异常。因此，注射Ad2CMV - Gp100至少部分通过细胞因子调节预防了EMIU的发生。
