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

Abu-Shah, Enas; Demetriou, Philippos; Bálint, Štefan; Mayya, Viveka; Kutuzov, Mikhail A; Dushek, Omer; Dustin, Michael L · Elife · 2019

basic_science · Level V

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Abstract

Research in the field of human immunology is restricted by the lack of a system that reconstitutes the <i>in-situ</i>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.

Medical subject headings