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

Elife. 2019 Sep 25:8: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-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.

Keywords: 3D model system; T-cells; TCR engineering; antigen presenting cells; human; human biology; immunology; immunotherapy; inflammation; medicine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigen Presentation / immunology
  • Antigen-Presenting Cells / immunology
  • Antigens / immunology
  • CD4-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Communication / immunology*
  • Cells, Cultured
  • Cytokines / immunology
  • Cytokines / metabolism
  • Dendritic Cells / immunology*
  • Humans
  • Immune System / cytology
  • Immune System / immunology
  • Immune System / metabolism
  • Lymphocyte Activation / immunology*

Substances

  • Antigens
  • Cytokines