Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells

• Published in: Journal of hepatology 2008-12, Vol.49 (6), p.1008-1018
• Main Authors: Tokita, Daisuke, Sumpter, Tina L, Raimondi, Giorgio, Zahorchak, Alan F, Wang, Zhiliang, Nakao, Atsunori, Mazariegos, George V, Abe, Masanori, Thomson, Angus W
• Format: Article
• Language: English
• Subjects: Animals; Apoptosis - immunology; B7-2 Antigen - metabolism; Biological and medical sciences; Calcium-Binding Proteins - metabolism; CD4 Antigens - metabolism; Cell Communication - immunology; Cell Differentiation - immunology; Dendritic cells; Dendritic Cells - cytology; Dendritic Cells - immunology; Dendritic Cells - metabolism; Endotoxin; Flow Cytometry; Gastroenterology and Hepatology; Gastroenterology. Liver. Pancreas. Abdomen; Histocompatibility Antigens Class II - metabolism; Immune Tolerance - immunology; Intercellular Signaling Peptides and Proteins - metabolism; Interleukin-10 - metabolism; Interleukin-12 - metabolism; Interleukin-2 Receptor alpha Subunit - metabolism; Jagged-1 Protein; Lipopolysaccharides - pharmacology; Liver; Liver - cytology; Liver - immunology; Male; Medical sciences; Membrane Proteins - metabolism; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mouse; Serrate-Jagged Proteins; Spleen - cytology; Spleen - immunology; T cells; T-Lymphocytes, Regulatory - cytology; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; Th2 Cells - cytology; Th2 Cells - immunology; Th2 Cells - metabolism; Tolerance; Toll-like receptor; Toll-Like Receptor 4 - metabolism
• ISSN: 0168-8278; 1600-0641
• DOI: 10.1016/j.jhep.2008.07.028

Background/Aims The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), – innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Methods Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg). Results While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4+ T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4+ CD25+ regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. Conclusions The inferior T cell allostimulatory activity of in vivo -stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity.