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

eLife (2019-09-26)
Enas Abu-Shah, Philippos Demetriou, Štefan Bálint, Viveka Mayya, Mikhail A Kutuzov, Omer Dushek, Michael L Dustin
RESUMEN

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.

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Human IgG, Fc Fragment