Monocyte-derived dendritic cells from cirrhotic patients retain similar capacity for maturation/activation and antigen presentation as those from healthy subjects

• Published in: Cellular immunology Vol. 295; no. 1; pp. 36 - 45
• Main Authors: Tanoue, Shiroh, Chang, Li-Yuan, Li, Yonghai, Kaplan, David E.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier Inc 01.05.2015
• Subjects: Adult; Aged; Antigen Presentation - immunology; Cell Differentiation - immunology; Cell Proliferation; Cells, Cultured; Cirrhosis; Coculture Techniques; Dendritic cell; Dendritic Cells - immunology; Dendritic Cells - metabolism; Enzyme-Linked Immunospot Assay; Flow Cytometry; Glypican-3; Healthy Volunteers; Hepatitis C; Human; Humans; Immunophenotyping; Interferon-gamma - immunology; Interferon-gamma - metabolism; Lipopolysaccharide Receptors - immunology; Lipopolysaccharide Receptors - metabolism; Liver Cirrhosis - immunology; Liver Cirrhosis - metabolism; Liver Cirrhosis - pathology; M1 macrophage; M2 macrophage; Macrophages - classification; Macrophages - immunology; Male; Middle Aged; Monocyte; Monocytes - immunology; Monocytes - metabolism; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Human; Dendritic cell; Monocyte; MoDC; M1 macrophage; HCC; AFP; CIR; PBMC; Cirrhosis; M2 macrophage; GPC3; HCV; Glypican-3; HD; Hepatitis C
• DOI: 10.1016/j.cellimm.2015.02.008
• ISSN: 0008-8749; 1090-2163

•CD14+ monocytes from cirrhotic patients displayed enhanced M1 and M2 polarization.•MoDC derived from cirrhotic CD14+ monocytes display normal co-stimulation markers.•Antigen-presentation capacity of MoDC from cirrhotic and healthy donors were similar. Few studies have investigated the impact of liver cirrhosis on dendritic cell function. The purpose of this study was to compare the activation and antigen-presentation capacity of monocyte-derived dendritic cells (MoDC) from cirrhotic patients (CIR) relative to healthy donors (HD). MoDC from CIR and HD were matured, phenotyped, irradiated and pulsed with 15mer peptides for two hepatocellular carcinoma-related antigens, alphafetoprotein and glypican-3, then co-cultured with autologous T-cells. Expanded T-cells were evaluated by interferon-gamma ELISPOT and intracellular staining. 15 CIR and 7 HD were studied. While CD14+ monocytes from CIR displayed enhanced M2 polarization, under MoDC-polarizing conditions, we identified no significant difference between HD and CIR in maturation-induced upregulation of co-stimulation markers. Furthermore, no significant differences were observed between CIR and HD in subsequent expansion of tumor antigen-specific IFNγ+ T-cells. Conclusion: MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors.