Miniaturized High-Throughput Multiparameter Flow Cytometry Assays Measuring In Vitro Human Dendritic Cell Maturation and T-Cell Activation in Mixed Lymphocyte Reactions

SLAS Discov. 2018 Aug;23(7):742-750. doi: 10.1177/2472555218775409. Epub 2018 Jun 6.

Abstract

Enhancing antitumor activities of the human immune system is a clinically proven approach with the advent of monoclonal antibodies recognizing programmed cell death protein-1 (PD1) receptors on immune cell surfaces. Historically, using flow cytometry as a means to assess next-generation agent activities was underused, largely due to limits on cell number and assay sensitivity. Here, we leveraged an IntelliCyt high-throughput flow cytometry platform to monitor human dendritic cell maturation and lymphocyte proliferation in mixed lymphocyte reactions. Specifically, we established flow cytometry-based immunophenotyping and screening methodologies capable of measuring T-cell activation as a result of cell-associated antigens presented on dendritic cell surfaces, as indicated by cell proliferation, cytokine secretion, and surface marker expression. Together, the overall novelty of this 384-well platform is its capability to measure multiple functional readouts in one well and consistently evaluate large numbers of compounds in a single study, as well as its ability to show increased assay sensitivity requiring considerably fewer primary cells and less reagents compared to more traditional 96-well flow cytometry methods.

Keywords: IntelliCyt; MLR; T cell; dendritic cell; flow cytometry; mixed lymphocyte reaction.

MeSH terms

  • Cytokines / metabolism
  • Dendritic Cells / immunology
  • Dendritic Cells / metabolism*
  • Flow Cytometry* / methods
  • High-Throughput Screening Assays*
  • Humans
  • Lymphocyte Activation* / immunology
  • Lymphocyte Culture Test, Mixed*
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*

Substances

  • Cytokines