Journal
HUMAN IMMUNOLOGY
Volume 72, Issue 1, Pages 24-31Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.humimm.2010.10.004
Keywords
Dendritic cell; IL-12; T helper cell; Toll-like receptor; Innate immunity
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Funding
- National Institutes of Health/National Center for Research Resources [UL 1RR024989]
- [R01 CA100163]
- NATIONAL CANCER INSTITUTE [R01CA100163] Funding Source: NIH RePORTER
- NATIONAL CENTER FOR RESEARCH RESOURCES [UL1RR024989] Funding Source: NIH RePORTER
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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)-gamma, 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-gamma 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-gamma-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. (c) 2011 American Society for Histocompatibility and Immunogenetics. Published by Elsevier Inc. All rights reserved.
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