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


CONCLUSIONS
MoDCs isolated from cirrhotic individuals retain similar capacity for in vitro activation, maturation and antigen-presentation as those from healthy donors.
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Shiroh
S
Tanoue
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Li-Yuan
LY
Chang
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA.
Yonghai
Y
Li
Medicine and Research Services, Philadelphia VA Medical Center, 3900 Woodland Avenue, Philadelphia, PA 19104, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, 914 BRB, 421 Curie Blvd., Philadelphia, PA 19104, USA. Electronic address: dakaplan@mail.med.upenn.edu.
David E
DE
Kaplan
D000328:Adult; D000368:Aged; D017951:Antigen Presentation / Q000276:immunology*; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D058501:Enzyme-Linked Immunospot Assay; D005434:Flow Cytometry; D064368:Healthy Volunteers; D006801:Humans; D016130:Immunophenotyping; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D018950:Lipopolysaccharide Receptors / Q000276:immunology / Q000378:metabolism; D008103:Liver Cirrhosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000145:classification / Q000276:immunology; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000276:immunology* / Q000378:metabolism; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism
D018950:Lipopolysaccharide Receptors; D007371:Interferon-gamma
Cirrhosis; Dendritic cell; Glypican-3; Hepatitis C; Human; M1 macrophage; M2 macrophage; Monocyte