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

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Cite this article as: eLife 2019;8:e48221 doi: 10.7554/eLife.48221

Abstract

Research in the field of human immunology is restricted by the lack of a system that reconstitutes the in-situ 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 help to CD8 T-cells through enhanced maturation of DCs and effect of PD-1 checkpoint blockades. In addition, we characterise unique dynamics of T-cell/DC interactions as a function of antigen affinity.

Data availability

No new gene datasets were generated during this study. Source data files have been provided for Figures 2, 3, and 4. The TCR sequences used have been published in the past in the literature (cited in the manuscript) and the modifications made are clearly stated in the tables in the manuscript. The constructs are available through a request to the corresponding authors of the previously published articles.

Article and author information

Author details

  1. Enas Abu Shah

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    For correspondence
    enas.abushah@path.ox.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5033-8171
  2. Philippos Demetriou

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  3. Štefan Bálint

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4470-5881
  4. Viveka Mayya

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  5. Mikhail A Kutuzov

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    Competing interests
    No competing interests declared.
  6. Omer Dushek

    Sir William Dunn School of Pathology, University of Oxford, Oxford, United Kingdom
    For correspondence
    omer.dushek@path.ox.ac.uk
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-5847-5226
  7. Michael L Dustin

    Kennedy Institute of Rheumatology, University of Oxford, Oxford, United Kingdom
    For correspondence
    michael.dustin@kennedy.ox.ac.uk
    Competing interests
    Michael L Dustin, Reviewing editor, eLife.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4983-6389

Funding

Wellcome Trust (100262Z/12/Z)

  • Michael L Dustin

Wellcome Trust (207537/Z/17/Z)

  • Omer Dushek

European Research Council (ERC-2014-AdG_670930)

  • Štefan Bálint
  • Viveka Mayya

Human Frontier Science Program (RGP0033/2015)

  • Michael L Dustin

UCB-Oxford

  • Enas Abu Shah

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Ethics

Human subjects: This project has been approved by the Medical Sciences Inter-Divisional Research Ethics Committee of the University of Oxford REC 11/H0711/7 to cover the use of human blood products purchased from National Health Services Blood and Transplant service (NHS England).

Reviewing Editor

  1. Shimon Sakaguchi, Osaka University, Japan

Publication history

  1. Received: May 6, 2019
  2. Accepted: September 24, 2019
  3. Accepted Manuscript published: September 25, 2019 (version 1)
  4. Version of Record published: December 12, 2019 (version 2)

Copyright

© 2019, Abu Shah et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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