G5 Dynamiques des Réponses Immunes, Institut Pasteur, 75015 Paris, France.
Proc Natl Acad Sci U S A. 2010 Feb 23;107(8):3675-80. doi: 10.1073/pnas.0905901107. Epub 2010 Feb 4.
In vitro studies have revealed that T cell activation occurs during the formation of either dynamic or stable interactions with antigen-presenting cells (APC), and the respective cell junctions have been referred to as immunological kinapses and synapses. However, the relevance and molecular dynamics of kinapses and synapses remain to be established in vivo. Using two-photon imaging, we tracked the distribution of LAT-EGFP molecules during antigen recognition by activated CD4(+) T cells in lymph nodes. At steady state, LAT-EGFP molecules were preferentially found at the uropod of rapidly migrating T cells. In contrast to naïve T cells that fully stopped upon systemic antigen delivery, recently activated T cells decelerated and formed kinapses, characterized by continuous extension of membrane protrusions and by the absence of persistent LAT-EGFP clustering. On the other hand, activated CD4(+) T cells formed stable immunological synapses with antigen-loaded B cells and displayed sustained accumulation of LAT-EGFP fluorescence at the contact zone. Our results show that the state of T cell activation and the type of APC largely influence T cell-APC contact dynamics in lymph nodes. Furthermore, we provide a dynamic look at immunological kinapses and synapses in lymph nodes and suggest the existence of distinct patterns of LAT redistribution during antigen recognition.
在体外研究中发现，T 细胞的激活发生在与抗原呈递细胞（APC）形成动态或稳定相互作用的过程中，相应的细胞连接分别被称为免疫连接点和突触。然而，在体内，连接点和突触的相关性和分子动力学仍有待确定。我们使用双光子成像技术，跟踪了激活的 CD4(+)T 细胞在淋巴结中识别抗原时 LAT-EGFP 分子的分布。在稳定状态下，LAT-EGFP 分子优先存在于快速迁移的 T 细胞的尾足处。与全身抗原递送后完全停止的幼稚 T 细胞不同，最近激活的 T 细胞减速并形成连接点，其特征是膜突起的连续延伸，以及没有持续的 LAT-EGFP 聚集。另一方面，激活的 CD4(+)T 细胞与负载抗原的 B 细胞形成稳定的免疫突触，并在接触区显示出持续积累的 LAT-EGFP 荧光。我们的结果表明，T 细胞激活状态和 APC 类型在很大程度上影响了淋巴结中 T 细胞与 APC 的接触动力学。此外，我们提供了淋巴结中免疫连接点和突触的动态视图，并提出了在抗原识别过程中 LAT 重新分布的不同模式的存在。
