Visualizing the Functional Diversification of CD8+ T Cell Responses in Lymph Nodes
Visualizing the Functional Diversification of CD8+ T Cell Responses in Lymph Nodes
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DOI：
10.1016/j.immuni.2010.08.016
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发表时间：
2010-09-24
期刊：
影响因子：
32.4
通讯作者：
Bousso, Philippe
中科院分区：
文献类型：
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作者：
Beuneu, Helene;Lemaitre, Fabrice;Bousso, Philippe
CD8(+) T细胞应答产生具有不同功能潜能的效应细胞，但该过程中早期事件的作用尚不明确。在此，我们对在淋巴结启动过程中表达干扰素 -γ（IFN -γ）基因座激活荧光报告基因的T细胞进行了成像。我们已经证明，在稳定的T细胞 - 树突状细胞（DC）接触过程中，基因激活效率存在显著差异，这在一定程度上受信号强度的影响。对首次细胞分裂进行成像时，我们发现当T细胞开始克隆扩增时，T细胞功能潜能的异质性就已非常明显。此外，通过在体外分析单个活化T细胞的命运，我们提供的证据表明，这些早期差异导致产生了具有不同功能特性的克隆后代。因此，淋巴结中早期的T细胞 - DC相互作用通过产生功能不同的克隆后代，在很大程度上导致了T细胞应答的异质性。
CD8(+) T cell responses generate effector cells endowed with distinct functional potentials but the contribution of early events in this process is unclear. Here, we have imaged T cells expressing a fluorescent reporter for the activation of the interferon-gamma (IFN-gamma) locus during priming in lymph nodes. We have demonstrated marked differences in the efficiency of gene activation during stable T cell-dentritic cell (DC) contacts, influenced in part by signal strength. Imaging the first cell division, we have demonstrated that heterogeneity in T cell functional potential was largely apparent as T cells initiated clonal expansion. Moreover, by analyzing the fate of single activated T cells ex vivo, we have provided evidence that these early differences resulted in clonal progenies with distinct functional properties. Thus, the early set of T cell-DC interactions in lymph nodes largely contribute to the heterogeneity of T cell responses through the generation of functionally divergent clonal progenies.