In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages
In vivo imaging of CD8+ T cell-mediated elimination of malaria liver stages
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DOI：
10.1073/pnas.1303858110
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发表时间：
2013-05-28
影响因子：
11.1
通讯作者：
Menard, Robert
中科院分区：
文献类型：
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作者：
Cockburn, Ian A.;Amino, Rogerio;Menard, Robert
CD8（+）T细胞是适应性免疫系统的特化细胞，能够发现和消除病原体感染的细胞。到目前为止，还没有可能观察到任何病原体的破坏由CD8（+）T细胞在体内。在这里，我们展示了一种技术，用于成像杀死肝脏阶段的疟疾寄生虫的CD8（+）T细胞携带转基因T细胞受体特异性的寄生虫表位。我们报告了几个特征，还没有被描述的过程中，在体外分析，主要是在感染的肝细胞周围的效应CD8（+）T细胞的大集群的形成。簇的形成需要抗原特异性CD8（+）T细胞和G蛋白偶联受体的信号传导，尽管不相关特异性的CD8（+）T细胞也被募集到簇中。通过结合数学建模和数据分析，我们认为簇的形成主要是由T细胞增强募集成更大的簇驱动的。我们进一步展示了寄生虫的各种死亡表型，这些表型通常伴随着感染的肝细胞和CD8（+）T细胞之间的长期相互作用。这些发现强调需要活体成像来剖析病原体识别和CD8（+）T细胞杀伤的精细机制。
CD8(+) T cells are specialized cells of the adaptive immune system capable of finding and eliminating pathogen-infected cells. To date it has not been possible to observe the destruction of any pathogen by CD8(+) T cells in vivo. Here we demonstrate a technique for imaging the killing of liver-stage malaria parasites by CD8(+) T cells bearing a transgenic T cell receptor specific for a parasite epitope. We report several features that have not been described by in vitro analysis of the process, chiefly the formation of large clusters of effector CD8(+) T cells around infected hepatocytes. The formation of clusters requires antigen-specific CD8(+) T cells and signaling by G protein-coupled receptors, although CD8(+) T cells of unrelated specificity are also recruited to clusters. By combining mathematical modeling and data analysis, we suggest that formation of clusters is mainly driven by enhanced recruitment of T cells into larger clusters. We further show various death phenotypes of the parasite, which typically follow prolonged interactions between infected hepatocytes and CD8(+) T cells. These findings stress the need for intravital imaging for dissecting the fine mechanisms of pathogen recognition and killing by CD8(+) T cells.