4.8 Article

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

Journal

ELIFE
Volume 8, Issue -, Pages -

Publisher

ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/eLife.48221

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Funding

  1. Wellcome Trust [100262Z/12/Z, 207537/Z/17/Z]
  2. UCB UK UCB-Oxford [AZR00960]
  3. European Research Council [ERC-2014-AdG_670930]
  4. Human Frontier Science Program [RGP0033/2015]
  5. Kennedy Trust for Rheumatology
  6. Wellcome Trust [207537/Z/17/Z] Funding Source: Wellcome Trust

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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.

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