DC Respond to Cognate T Cell Interaction in the Antigen-Challenged Lymph Node
DC Respond to Cognate T Cell Interaction in the Antigen-Challenged Lymph Node
复制标题
DOI：
10.3389/fimmu.2019.00863
复制
发表时间：
2019-04-25
影响因子：
7.3
通讯作者：
Jung, Steffen
中科院分区：
文献类型：
--
作者：
Curato, Caterina;Bernshtein, Biana;Jung, Steffen
树突状细胞（DC）在通过呈递抗原和提供共刺激来引发幼稚T细胞的潜力方面是无与伦比的。此外，DC被认为凭借模式识别受体解码抗原背景，并通过细胞因子分泌朝向不同的效应子功能激活T细胞。不同极化的T辅助细胞（T-H）已被详细研究。相反，迄今为止，指导DC的研究主要限于体外环境或过继转移的DC。在这里，我们报告的努力，以解开同源T细胞在抗原挑战的淋巴结（LN）遇到的DC反应。用包埋佐剂的纳米颗粒（NP）免疫移植有抗原特异性T细胞的小鼠，并用抗原吸收，以使用本体和单细胞RNA-seq分析来研究DC对T细胞相遇的立即应答。NP诱导强的抗原特异性T（H）1细胞应答，具有最小的旁观者激活。荧光标记的NP允许识别携带抗原的DC，并专注于遇到T细胞的DC中的转录变化。我们的研究结果支持DC和T细胞之间存在促进T（H）1应答的双向串扰，包括泛素样分子Isg 15的参与，值得进一步研究。
Dendritic cells (DC) are unrivaled in their potential to prime naive T cells by presenting antigen and providing costimulation. DC are furthermore believed to decode antigen context by virtue of pattern recognition receptors and to polarize T cells through cytokine secretion toward distinct effector functions. Diverse polarized T helper (T-H) cells have been explored in great detail. In contrast, studies of instructing DC have to date largely been restricted to in vitro settings or adoptively transferred DC. Here we report efforts to unravel the DC response to cognate T cell encounter in antigen-challenged lymph nodes (LN). Mice engrafted with antigen-specific T cells were immunized with nanoparticles (NP) entrapping adjuvants and absorbed with antigen to study the immediate DC response to T cell encounter using bulk and single cell RNA-seq profiling. NP induced robust antigen-specific T(H)1 cell responses with minimal bystander activation. Fluorescent-labeled NP allowed identification of antigen-carrying DC and focus on transcriptional changes in DC that encounter T cells. Our results support the existence of a bi-directional crosstalk between DC and T cells that promotes T(H)1 responses, including involvement of the ubiquitin-like molecule Isg15 that merits further study.