Discriminating Protective from Nonprotective Plasmodium-Specific CD8+ T Cell Responses.
Discriminating Protective from Nonprotective Plasmodium-Specific CD8+ T Cell Responses.
复制标题
DOI：
10.4049/jimmunol.1600155
复制
发表时间：
2016-05-15
期刊：
影响因子：
--
通讯作者：
Harty JT
中科院分区：
文献类型：
--
作者：
Doll KL;Pewe LL;Kurup SP;Harty JT
尽管经过几十年的研究，疟疾仍然是一个全球性的健康危机。目前的亚单位疫苗方法不能提供针对人类疟原虫感染的有效的长期、杀菌免疫。相反，具有更大的靶抗原阵列的全寄生虫疫苗接种赋予了人类持久的杀菌保护。在啮齿动物疟疾模型中的类似研究表明，CD 8 + T细胞在整个寄生虫疫苗接种后的肝脏阶段免疫中发挥关键作用。然而，目前尚不清楚是否所有的CD 8 + T细胞特异性引起的整个寄生虫疫苗接种有助于保护，一个问题的增强亚单位疫苗接种的重要意义。在这里，我们显示了在小鼠中针对伯氏疟原虫GAP 5041 -48、S20318-325、TRAP 130 -138或CSP 252 -260蛋白衍生表位的初免-加强免疫后，相似表型的稳健的CD 8 + T细胞应答增加，但只有CSP 252 -260-和TRAP 130 -138-特异性CD 8 + T细胞提供杀菌免疫并减少子孢子攻击后的肝寄生虫负荷。此外，子孢子表面表达的CSP和TRAP蛋白特异性的CD 8 + T细胞，但不是细胞内GAP 50和S20蛋白，在体外被子孢子感染的肝细胞有效识别。这些结果表明：1）保护相关的抗原靶标，无论其免疫原性潜力如何，必须由感染的肝细胞有效地呈递给CD 8 + T细胞以消除肝期疟原虫感染; 2）子孢子表面表达的蛋白质可能是保护性CD 8 + T细胞的良好靶抗原。
Despite decades of research, malaria remains a global health crisis. Current subunit vaccine approaches do not provide efficient long-term, sterilizing immunity against Plasmodium infections in humans. Conversely, whole parasite vaccinations with their larger array of target antigens have conferred long lasting sterilizing protection to humans. Similar studies in rodent models of malaria reveal that CD8+ T cells play a critical role in liver-stage immunity after whole parasite vaccination. However, it is unknown whether all CD8+ T cell specificities elicited by whole parasite vaccination contribute to protection, an issue of great relevance for enhanced subunit vaccination. Here we show that robust CD8+ T cell responses of similar phenotype are mounted following prime-boost immunization against Plasmodium berghei GAP5041-48, S20318-325, TRAP130-138 or CSP252-260 protein-derived epitopes in mice, but only CSP252-260- and TRAP130-138-specific CD8+ T cells provide sterilizing immunity and reduce liver parasite burden following sporozoite challenge. Further, CD8+ T cells specific to sporozoite surface-expressed CSP and TRAP proteins, but not the intracellular GAP50 and S20 proteins, are efficiently recognized by sporozoite-infected hepatocytes in vitro. These results suggest that 1) protection-relevant antigenic targets, regardless of their immunogenic potential, must be efficiently presented by infected hepatocytes for CD8+ T cells to eliminate liver-stage Plasmodium infection and 2) proteins expressed on the surface of sporozoites may be good target antigens for protective CD8+ T cells.