Murine liver plasmacytoid dendritic cells become potent immunostimulatory cells after Flt-3 ligand expansion.
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-alpha and low IL-10 secretion. To facilitate the investigation of murine liver pDCs, we expanded them in vivo with fms-like tyrosine kinase 3 ligand (Flt3L). After Toll-like receptor-9 ligation, expanded liver pDCs secreted high levels of IFN-alpha 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.


CONCLUSIONS
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.
Kingham
T Peter
TP
Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA.
Chaudhry
Umer I
UI
Plitas
George
G
Katz
Steven C
SC
Raab
Jesse
J
DeMatteo
Ronald P
RP
D000818:Animals; D000954:Antigens, Surface / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000276:immunology / Q000502:physiology*; D007108:Immune Tolerance / Q000502:physiology; D007114:Immunization / Q000379:methods*; D016898:Interferon-alpha / Q000378:metabolism; D037181:Lectins, C-Type / Q000378:metabolism; D008099:Liver / Q000166:cytology / Q000276:immunology*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D055651:NK Cell Lectin-Like Receptor Subfamily B; D013154:Spleen / Q000166:cytology / Q000276:immunology
D000954:Antigens, Surface; D016898:Interferon-alpha; D037181:Lectins, C-Type; D008565:Membrane Proteins; D055651:NK Cell Lectin-Like Receptor Subfamily B; C084881:flt3 ligand protein