Effect of multiple activation stimuli on the generation of Th1-polarizing dendritic cells

Christopher Paustian, Richard Caspell, Terrence Johnson, Peter A. Cohen, Suyu Shu, Shuwen Xu, Brian J. Czerniecki, Gary K. Koski

Research output: Contribution to journalArticle

21 Scopus citations

Abstract

It was originally reported that only a small fraction of total matured dendritic cells (DCs) produced interleukin (IL)-12, but it has never been determined whether different combinations of activating signals now shown to maximize secreted IL-12 do so through increasing output by the same IL-12 producers, or by recruiting additional cytokine-secreting cells. We therefore tested all combinations of bacterial lipopolysaccharide (LPS) (TLR4 ligand), R848 (TLR8 ligand), interferon (IFN)-γ, and CD40L for activating human monocyte-derived dendritic cells (DC), and determined by intracellular flow cytometry that enhanced IL-12 secretion was accomplished in large part by markedly increasing the proportion of cells producing IL-12, with the triple and quadruple combinations recruiting the most DC. This optimization requirement for multiple signals was not reflected in differential Toll-like receptor (TLR) expression by the cells. Interestingly, DCs activated with single TLR ligands plus IFN-γ were capable of responding with a second burst of IL-12 upon later CD40L stimulation, whereas DCs activated with R848 plus LPS were not, despite the trend of the latter for superior polarization of naive T cells toward IFN-γ-secreting Th1. These results have implications for the biology of IL-12-secreting DCs and choice of activation regimen for prospective use in DC-based immunotherapy.

Original languageEnglish (US)
Pages (from-to)24-31
Number of pages8
JournalHuman Immunology
Volume72
Issue number1
DOIs
StatePublished - Jan 1 2011

Keywords

  • Dendritic cell
  • IL-12
  • Innate immunity
  • T helper cell
  • Toll-like receptor

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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    Paustian, C., Caspell, R., Johnson, T., Cohen, P. A., Shu, S., Xu, S., Czerniecki, B. J., & Koski, G. K. (2011). Effect of multiple activation stimuli on the generation of Th1-polarizing dendritic cells. Human Immunology, 72(1), 24-31. https://doi.org/10.1016/j.humimm.2010.10.004