Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver.
Immunization with genetically attenuated P52-deficient Plasmodium berghei sporozoites induces a long-lasting effector memory CD8+ T cell response in the liver.
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DOI：
10.1186/1476-8518-9-6
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发表时间：
2011-10-17
期刊：
影响因子：
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通讯作者：
Epiphanio S
中科院分区：
文献类型：
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作者：
Douradinha B;van Dijk M;van Gemert GJ;Khan SM;Janse CJ;Waters AP;Sauerwein RW;Luty AJ;Silva-Santos B;Mota MM;Epiphanio S
通过γ射线或基因缺失减毒的子孢子进行免疫接种，可以有效地诱导无菌免疫和持久的抗疟疾保护。对于用辐射减毒子孢子（RAS）免疫的小鼠，已经显示肝内效应记忆CD 8 + T细胞对于保护是关键的。最近的研究表明，小鼠中遗传减毒寄生虫（GAP）的免疫也由肝脏效应记忆CD 8 + T细胞赋予。在这项研究中，我们分析了缺乏P52蛋白的GAP免疫后的效应记忆细胞反应。我们证明，免疫接种p52-GAP子孢子也导致效应记忆CD 8 + T细胞的强烈增加，甚至在免疫接种后6个月，而没有特异性的CD 4+效应T细胞反应可以检测到。此外，我们表明效应记忆CD 8 + T细胞的增加是特异性的肝脏，而不是脾或淋巴结。这些结果表明，用伯氏疟原虫p52-GAP免疫小鼠产生的免疫应答与由缺乏UIS 3或UIS 4表达的RAS或GAP诱导的免疫应答相当，其中涉及肝内效应记忆CD 8 + T细胞的重要作用。了解不同GAP免疫后保护性免疫的介质对于进一步开发由遗传减毒子孢子组成的疫苗是重要的。
The induction of sterile immunity and long lasting protection against malaria has been effectively achieved by immunization with sporozoites attenuated by gamma-irradiation or through deletion of genes. For mice immunized with radiation attenuated sporozoites (RAS) it has been shown that intrahepatic effector memory CD8+ T cells are critical for protection. Recent studies have shown that immunization with genetically attenuated parasites (GAP) in mice is also conferred by liver effector memory CD8+ T cells. In this study we analysed effector memory cell responses after immunization of GAP that lack the P52 protein. We demonstrate that immunization with p52-GAP sporozoites also results in a strong increase of effector memory CD8+ T cells, even 6 months after immunization, whereas no specific CD4+ effector T cells response could be detected. In addition, we show that the increase of effector memory CD8+ T cells is specific for the liver and not for the spleen or lymph nodes. These results indicate that immunization of mice with P. berghei p52-GAP results in immune responses that are comparable to those induced by RAS or GAP lacking expression of UIS3 or UIS4, with an important role implicated for intrahepatic effector memory CD8+ T cells. The knowledge of the mediators of protective immunity after immunization with different GAP is important for the further development of vaccines consisting of genetically attenuated sporozoites.