A synaptic basis for paracrine interleukin-2 signaling during homotypic T cell interaction.
A synaptic basis for paracrine interleukin-2 signaling during homotypic T cell interaction.
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DOI：
10.1016/j.immuni.2008.05.017
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发表时间：
2008-08-15
期刊：
影响因子：
32.4
通讯作者：
Krummel, Matthew F.
中科院分区：
文献类型：
--
作者：
Sabatos, Catherine A.;Doh, Junsang;Chakravarti, Sumone;Friedman, Rachel S.;Pandurangi, Priya G.;Tooley, Aaron J.;Krummel, Matthew F.
T细胞在遇到携带肽-MHC复合物的抗原呈递细胞（APC）后减慢其运动性，增加粘附和停滞。在这里，我们分析了活化T细胞之间的细胞间通讯。在体内和体外，活化T细胞以大簇的形式结合，集体持续超过30分钟，但它们也参与了更短暂的相互作用，显然在APC的远端。同型聚集由LFA-1整联蛋白相互作用驱动。超微结构分析显示，活化T细胞之间的细胞-细胞接触组织为多灶性突触，和T细胞的微管组织复合物和白细胞介素-2（IL-2）的分泌朝向这个突触。相对于游离细胞，参与同型相互作用的T细胞更有效地捕获IL-2。接受旁分泌突触IL-2的T细胞将其IL-2信号亚基极化到突触区域，并更有效地磷酸化转录因子STAT 5，可能是通过突触相关的信号复合物。因此，突触介导的细胞因子递送加速了激活T细胞的反应。
T cells slow their motility, increase adherence and arrest after encounters with antigen-presenting cells (APCs) bearing peptide-MHC complexes. Here, we analyzed the cell-cell communication among activating T cells. In vivo and in vitro, activating T cells associate in large clusters that collectively persist for >30 minutes, but they also engaged in more transient interactions, apparently distal to APCs. Homotypic aggregation was driven by LFA-1 integrin interactions. Ultrastructural analysis revealed that cell-cell contacts between activating T cells were organized as multifocal synapses, and T cells oriented both the microtubule organizing complex and interleukin-2 (IL-2) secretion toward this synapse. T cells engaged in homotypic interactions more effectively captured IL-2 relative to free cells. T cells receiving paracrine synaptic IL-2 polarized their IL-2 signaling subunits into the synaptic region and more efficiently phosphorylated the transcription factor STAT5, likely through a synapse-associated signaling complex. Thus, synapse-mediated cytokine delivery accelerates responses in activating T cells.
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影响因子：
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作者：
Brossard, C;Feuillet, V;Trautmann, A
通讯作者：
Trautmann, A
影响因子：
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Hugues, Stephanie;Scholer, Alix;Fetler, Luc
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Fetler, Luc
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作者：
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