Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion Journal Article

  

Authors:	Kingham, T. P.; Chaudhry, U. I.; Plitas, G.; Katz, S. C.; Raab, J.; DeMatteo, R. P.
Article Title:	Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion
Abstract:	The liver has unique immunological properties. Although dendritic cells (DCs) are central mediators of immune regulation, little is known about liver DCs. Plasmacytoid DCs (pDCs) are a recently identified subtype of murine liver DC. We sought to define the function of freshly isolated murine liver pDCs. We found that normal liver pDCs were weak in stimulating T cells, yet they possessed a proinflammatory cytokine profile with high tumor necrosis factor-α and low IL-10 secretion. To facilitate the investigation of murine liver pDCs, we expanded them in vivo with fins-like tyrosine kinase 3 ligand (Flt3L). After Toll-like receptor-9 ligation, expanded liver pDCs secreted high levels of IFN-α and were able to stimulate NK cells, NKT cells, and antigen-specific CD8+ T cells in vitro. In addition, Flt3L expansion alone generated pDCs capable of activating antigen-specific CD8 + T cells in vivo. Conclusion: Unstimulated liver pDCs exist in a latent state with the potential to become potent activators of the innate and adaptive immune systems through their interactions with other immune effectors. Our findings have implications for understanding the role of the liver in tolerance and immunity. Copyright © 2007 by the American Association for the Study of Liver Diseases.
Keywords:	controlled study; nonhuman; cd8 antigen; cell proliferation; t lymphocyte; cd8-positive t-lymphocytes; animal cell; mouse; phenotype; animals; mice; cells, cultured; cell function; spleen; dendritic cell; interleukin 10; animal experiment; membrane proteins; in vivo study; in vitro study; mice, inbred balb c; mice, inbred c57bl; mice, transgenic; cytokine; liver; dendritic cells; immune tolerance; tumor necrosis factor alpha; cell isolation; natural killer cell; immunostimulation; liver cell; antigens, surface; interferon-alpha; immunization; toll like receptor 9; cd135 antigen; lectins, c-type
Journal Title:	Hepatology
Volume:	45
Issue:	2
ISSN:	0270-9139
Publisher:	John Wiley & Sons
Date Published:	2007-02-01
Start Page:	445
End Page:	454
Language:	English
DOI:	10.1002/hep.21457
PUBMED:	17256750
PROVIDER:	scopus
DOI/URL:	http://www.scopus.com/inward/record.url?eid=2-s2.0-33847752705&partnerID=40&md5=4b655e08c6bfe8e5d606a9c6b8984640
Notes:	--- - "Cited By (since 1996): 19" - "Export Date: 17 November 2011" - "CODEN: HPTLD" - "Source: Scopus"