Norwegian School of Veterinary Science, Department of Basic Sciences and Aquatic Medicine, PO Box 8146 Dep., N-0033 Oslo, Norway.
Vaccine. 2013 Apr 8;31(15):1956-63. doi: 10.1016/j.vaccine.2013.02.008. Epub 2013 Feb 17.
Infectious pancreatic necrosis virus (IPNV) is a highly contagious disease causing high mortalities in juvenile salmonids. Lack of correlation between neutralizing antibodies and infecting virus suggests a likelihood of involvement of the cellular mediated immune response in vaccine protection. To elucidate the kinetics of CD4 and CD8 T-cells responses in vaccine protection, Atlantic salmon (Salmo salar L) were vaccinated with a high antigen (HiAg) or low antigen (LoAg) dose vaccine and challenged by cohabitation using a highly virulent Norwegian Sp strain. Analysis of T-cell gene expression in lymphoid organs (headkidney and spleen) showed that GATA-3 was positively correlated with increase in antibody levels when T-bet was low. Conversely, T-bet and FoxP3 were positively correlated with viral infection and negatively correlated with increase in antibody levels. Among the CD8+ T cell genes, expression of eomes and CD8α were positively correlated with increase in viral copy numbers and negatively correlated with increase in antibody levels. Up-regulation of granzyme A was highly correlated with increase in viral copy numbers in the LoAg and control groups indicating that this gene could save as a diagnostic marker of acute infection for IPNV during acute infection. In contrast, its down regulation in the HiAg which had low viral copy numbers corresponded with high antibody levels. Overall, these data show that the kinetics of CD4 and CD8 T-cell genes expression follow the same pattern as that observed in higher vertebrates. These findings suggest that functional signatures of the cellular mediated immune response could be evolutionary conserved across the vertebrate taxa and that they can effectively be used to monitor vaccine protection and infection progression of IPNV in Atlantic salmon.
传染性胰脏坏死病毒 (IPNV) 是一种高度传染性疾病，可导致幼年鲑鱼死亡率很高。中和抗体与感染病毒之间缺乏相关性表明，细胞介导的免疫反应可能参与疫苗保护。为了阐明 CD4 和 CD8 T 细胞反应在疫苗保护中的动力学，用高抗原（HiAg）或低抗原（LoAg）剂量疫苗对大西洋鲑（Salmo salar L）进行免疫接种，并通过同居用高度毒力的挪威 Sp 株进行攻毒。分析淋巴器官（头肾和脾脏）中的 T 细胞基因表达表明，当 T-bet 较低时，GATA-3 与抗体水平的升高呈正相关。相反，T-bet 和 FoxP3 与病毒感染呈正相关，与抗体水平的升高呈负相关。在 CD8+T 细胞基因中，eomes 和 CD8α 的表达与病毒拷贝数的增加呈正相关，与抗体水平的增加呈负相关。在 LoAg 和对照组中，颗粒酶 A 的上调与病毒拷贝数的增加高度相关，表明该基因可作为 IPNV 急性感染的诊断标志物。相比之下，在 HiAg 中，病毒拷贝数较低，与之对应的是抗体水平较高，颗粒酶 A 的下调。总的来说，这些数据表明 CD4 和 CD8 T 细胞基因表达的动力学与在高等脊椎动物中观察到的模式相同。这些发现表明，细胞介导的免疫反应的功能特征可能在脊椎动物分类群中具有进化保守性，并且可以有效地用于监测大西洋鲑中 IPNV 的疫苗保护和感染进展。
