Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situ 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 help to CD8 T-cells through enhanced maturation of DCs and effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.
No new gene datasets were generated during this study. Source data files have been provided for Figures 2, 3, and 4. The TCR sequences used have been published in the past in the literature (cited in the manuscript) and the modifications made are clearly stated in the tables in the manuscript. The constructs are available through a request to the corresponding authors of the previously published articles.
- Michael L Dustin
- Omer Dushek
- Štefan Bálint
- Viveka Mayya
- Michael L Dustin
- Enas Abu Shah
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Human subjects: This project has been approved by the Medical Sciences Inter-Divisional Research Ethics Committee of the University of Oxford REC 11/H0711/7 to cover the use of human blood products purchased from National Health Services Blood and Transplant service (NHS England).
- Shimon Sakaguchi, Osaka University, Japan
© 2019, Abu Shah et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.