eLife (Sep 2019)

A tissue-like platform for studying engineered quiescent human T-cells’ interactions with dendritic cells

  • Enas Abu-Shah,
  • Philippos Demetriou,
  • Štefan Bálint,
  • Viveka Mayya,
  • Mikhail A Kutuzov,
  • Omer Dushek,
  • Michael L Dustin

DOI
https://doi.org/10.7554/eLife.48221
Journal volume & issue
Vol. 8

Abstract

Read online

Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situactivation 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.

Keywords