Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions.
Robust Anti-viral Immunity Requires Multiple Distinct T Cell-Dendritic Cell Interactions.
复制标题
DOI：
10.1016/j.cell.2015.08.004
复制
发表时间：
2015-09-10
期刊：
影响因子：
64.5
通讯作者：
Kastenmüller W
中科院分区：
文献类型：
--
作者：
Eickhoff S;Brewitz A;Gerner MY;Klauschen F;Komander K;Hemmi H;Garbi N;Kaisho T;Germain RN;Kastenmüller W
宿主对病毒和细胞内寄生虫的防御依赖于效应CD 8 + T细胞，其最佳克隆扩增、分化和记忆特性需要来自CD 4 + T细胞的信号。在这里，我们解决了树突状细胞（DC）亚群在两种T细胞类型的初始激活和它们的合作的作用。令人惊讶的是，CD 4+和CD 8 + T细胞的初始引发在淋巴结内空间上分离，并且发生在不同的DC上，具有通过MHCI与MHCII分子的时间上不同的抗原呈递模式。在后期检测到通过两种MHC分子共呈递抗原的DC;这些XCR 1 +-DC是参与CD 8 + T细胞应答的CD 4 + T细胞增强的关键平台。这些研究结果描绘了复杂的编排的细胞相互作用的基础上有效的细胞介导的抗病毒反应，与基本的DC亚群生物学的影响，以及为翻译应用开发的疫苗，唤起最佳的T细胞免疫。
Host defense against viruses and intracellular parasites depends on effector CD8+ T cells whose optimal clonal expansion, differentiation, and memory properties require signals from CD4+ T cells. Here we addressed the role of dendritic cell (DC) subsets in initial activation of the two T cell types and their co-operation. Surprisingly, initial priming of CD4+ and CD8+ T cells was spatially segregated within the lymph node and occurred on different DC with temporally distinct patterns of antigen-presentation via MHCI vs. MHCII molecules. DC that co-present antigen via both MHC molecules were detected at a later stage; these XCR1+-DC are the critical platform involved in CD4+ T cell augmentation of CD8+ T cell responses. These findings delineate the complex choreography of cellular interactions underlying effective cell-mediated anti-viral responses, with implications for basic DC subset biology as well as for translational application to the development of vaccines that evoke optimal T cell immunity.