Deep-learning-based three-dimensional label-free tracking and analysis of immunological synapses of CAR-T cells

Elife. 2020 Dec 17:9:e49023. doi: 10.7554/eLife.49023.

Abstract

The immunological synapse (IS) is a cell-cell junction between a T cell and a professional antigen-presenting cell. Since the IS formation is a critical step for the initiation of an antigen-specific immune response, various live-cell imaging techniques, most of which rely on fluorescence microscopy, have been used to study the dynamics of IS. However, the inherent limitations associated with the fluorescence-based imaging, such as photo-bleaching and photo-toxicity, prevent the long-term assessment of dynamic changes of IS with high frequency. Here, we propose and experimentally validate a label-free, volumetric, and automated assessment method for IS dynamics using a combinational approach of optical diffraction tomography and deep learning-based segmentation. The proposed method enables an automatic and quantitative spatiotemporal analysis of IS kinetics of morphological and biochemical parameters associated with IS dynamics, providing a new option for immunological research.

Keywords: cell biology; chimeric antigen receptor T cells; deep learning; immunological synapse; immunology; inflammation; optical diffraction tomography; quantitative phase imaging.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Deep Learning*
  • Humans
  • Immunological Synapses / immunology*
  • K562 Cells
  • Receptors, Chimeric Antigen / immunology*
  • T-Lymphocytes / immunology*
  • Tomography, Optical

Substances

  • Receptors, Chimeric Antigen