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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.

Original publication

DOI

10.7554/eLife.48221

Type

Journal article

Journal

Elife

Publication Date

25/09/2019

Volume

8

Keywords

3D model system, T-cells, TCR engineering, antigen presenting cells, human, human biology, immunology, immunotherapy, inflammation, medicine, Antigen Presentation, Antigen-Presenting Cells, Antigens, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Cell Communication, Cells, Cultured, Cytokines, Dendritic Cells, Humans, Immune System, Lymphocyte Activation