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

Author:

Abu-Shah Enas12ORCID,Demetriou Philippos1,Bálint Štefan1ORCID,Mayya Viveka1ORCID,Kutuzov Mikhail A2,Dushek Omer2ORCID,Dustin Michael L13ORCID

Affiliation:

1. Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom

2. Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom

3. Skirball Institute of Biomolecular Medicine, New York University School of Medicine, New York, United States

Abstract

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.

Funder

Wellcome Trust

UCB UK

European Research Council

Human Frontier Science Program

Kennedy Trust for Rheumatology

Publisher

eLife Sciences Publications, Ltd

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine,General Neuroscience

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