T cell activation requires mitochondrial translocation to the immunological synapse
T cell activation requires mitochondrial translocation to the immunological synapse
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DOI：
10.1073/pnas.0703126104
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发表时间：
2007-09-04
影响因子：
11.1
通讯作者：
Hoth, Markus
中科院分区：
文献类型：
--
作者：
Quintana, Ariel;Schwindling, Christian;Hoth, Markus
辅助T细胞（T-h）活化是适应性免疫应答所必需的。T-h细胞和抗原呈递细胞之间的免疫突触（IS）的形成是T-h细胞活化的必要条件。IS的形成诱导了许多信号分子的极化和再分配；然而，我们对is细胞形成过程中细胞器的再分配知之甚少。我们发现IS的形成诱导细胞骨架-边缘线粒体重新分布到IS的附近。使用全内反射显微镜，我们发现刺激后，IS和线粒体之间的距离减小到< 200 nm。因此，靠近IS的线粒体比远离IS的线粒体吸收更多的Ca2+。线粒体向IS的重新分布是维持Ca2+跨质膜内流和Ca2+依赖性Th细胞活化所必需的。我们的研究结果表明，线粒体是IS信号复合体的一部分，它们靠近IS的定位是T-h细胞激活所必需的。
T helper (T-h) cell activation is required for the adaptive immune response. Formation of the immunological synapse (IS) between T-h cells and antigen-presenting cells is essential for Th cell activation. IS formation induces the polarization and redistribution of many signaling molecules; however, very little is known about organelle redistribution during IS formation in Th cells. We show that formation of the IS induced cytoskeleton-clepenclent mitochondrial redistribution to the immediate vicinity of the IS. Using total internal reflection microscopy, we found that upon stimulation, the distance between the IS and mitochondria was decreased to values < 200 nm. Consequently, mitochondria close to the IS took up more Ca2+ than the ones farther away from the IS. The redistribution of mitochondria to the IS was necessary to maintain Ca2+ influx across the plasma membrane and Ca2+-dependent Th cell activation. Our results suggest that mitochondria are part of the signaling complex at the IS and that their localization close to the IS is required for T-h cell activation.