Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom.
Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom.
Elife. 2019 Sep 25;8:e48221. doi: 10.7554/eLife.48221.
Research in the field of human immunology is restricted by the lack of a system that reconstitutes the activation dynamics of quiescent human antigen-specific T-cells interacting with dendritic cells. Here we report a tissue-like system that recapitulates the dynamics of engineered primary human immune cell. Our approach facilitates real-time single-cell manipulations, tracking of interactions and functional responses complemented by population-based measurements of cytokines, activation status and proliferation. As a proof of concept, we recapitulate immunological phenomenon such as CD4 T-cells' help to CD8 T-cells through enhanced maturation of DCs and the effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.
人类免疫学领域的研究受到缺乏能够重建与树突状细胞相互作用的静止人类抗原特异性 T 细胞激活动力学的系统的限制。在这里，我们报告了一种组织样系统，该系统可以再现工程化原发性人类免疫细胞的动力学。我们的方法实现了实时单细胞操作、相互作用和功能反应的跟踪，同时还进行了基于群体的细胞因子测量、激活状态和增殖测量。作为概念验证，我们再现了免疫现象，例如 CD4 T 细胞通过增强树突状细胞的成熟来帮助 CD8 T 细胞，以及 PD-1 检查点阻断的效果。此外，我们还描述了 T 细胞/树突状细胞相互作用作为抗原亲和力的函数的独特动力学。
