T Cell Polarity at the Immunological Synapse Is Required for CD154-Dependent IL-12 Secretion by Dendritic Cells
T Cell Polarity at the Immunological Synapse Is Required for CD154-Dependent IL-12 Secretion by Dendritic Cells
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DOI：
10.4049/jimmunol.1001501
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发表时间：
2010-12
期刊：
影响因子：
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通讯作者：
M. Tourret;S. Guégan;K. Chemin;Stéphanie Dogniaux;F. Miró;Armelle Bohineust;C. Hivroz
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文献类型：
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作者：
M. Tourret;S. Guégan;K. Chemin;Stéphanie Dogniaux;F. Miró;Armelle Bohineust;C. Hivroz
T淋巴细胞和树突状细胞（DC）之间的ag特异性相互作用导致T细胞和DC激活。CD154 （CD40配体）/CD40相互作用已被证明在这种功能性串扰中起主要作用，尽管不是排他性的。T细胞和树突细胞之间的相互作用是由免疫突触（IS）构建的，其特征是T细胞微管细胞骨架向相互作用的树突细胞极化。然而，T细胞极化在T细胞诱导的直流电活化中可能发挥的作用大多是未知的。在这项研究中，我们利用两种不同的工具来阻断T细胞极性（即微管解聚药物和非典型蛋白激酶C抑制剂），在人类模型中探讨了T细胞极性在cd154依赖性dc激活中的作用。我们发现CD154被募集并集中在人原代T细胞和自体dc之间形成的is上，并且这种募集需要T细胞在is上的极性。此外，我们发现IS处的T细胞极化控制dc中T细胞依赖的CD154-CD40信号传导以及dc中cd154依赖的IL-12分泌。这项研究表明，T细胞极性在CD4+ T细胞和dc之间的CD154/ cd40依赖性串扰中起关键作用。
Ag-specific interaction between T lymphocytes and dendritic cells (DCs) leads to both T cell and DC activation. CD154 (CD40 ligand)/CD40 interactions have been shown to play a major, although not exclusive, role in this functional cross-talk. Interactions between T cells and DCs are structured by an immunological synapse (IS), characterized by polarization of the T cell microtubule cytoskeleton toward the interacting DCs. Yet the role T cell polarization may play in T cell-induced DC activation is mostly unknown. In this study, we address the role of T cell polarity in CD154-dependent activation of DCs in a human model, using two different tools to block T cell polarity (i.e., a microtubule depolymerizing drug and an inhibitor of atypical protein kinase C). We show that CD154 is recruited and concentrated at the IS formed between human primary T cells and autologous DCs and that this recruitment requires T cell polarity at the IS. Moreover, we show that T cell polarization at the IS controls T cell-dependent CD154–CD40 signaling in DCs as well as CD154-dependent IL-12 secretion by DCs. This study shows that T cell polarity at the IS plays a key role in CD154/CD40-dependent cross-talk between CD4+ T cells and DCs.