Monocyte-derived dendritic cells from cirrhotic patients retain similar capacity for maturation/activation and antigen presentation as those from healthy subjects (HUM7P.290)

• Published in: The Journal of immunology (1950) Vol. 192; no. Supplement_1; pp. 184 - 184.7
• Main Authors: Kaplan, David, Tanoue, Shiroh
• Format: Journal Article
• Language: English
• Published: 01.05.2014
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.192.Supp.184.7

Defects in dendritic cell function have been implicated in impaired T-cell responses against chronic hepatitis viruses but few studies have investigated the impact of liver cirrhosis on DC function. The purpose of this study was to compare the activation and APC capacity of MoDC from cirrhotic relative to healthy donors. CD14+ monocytes isolated from PBMC from cirrhotic or healthy donors were matured with GM-CSF/IL-4 x 24h, then activated with TNF-α/IL-1β/IL-6/PGE2/GM-CSF/IL-4 x24h with pre- and post-activation phenotyping. MoDCs were irradiated to 30Gy and pulsed with 15mer peptide pools for two liver tumor antigens alphafetoprotein (AFP) and glypican-3 (GPC3) as well as 9-10mer peptides for CMV/EBV/influenza (CEF). Autologous T-cells purified from PBMC were plated with irradiated/pulsed DC (5:1) and expanded with IL-2, IL-15 and IL-21, refeeding on d13 and d20. Expanded T-cells were evaluated by IFNγ ELISPOT and intracellular cytokine staining on d27. 13 patients with cirrhosis (CIR) and 5 healthy age-matched donors (HD) were studied. No significant difference were identified in MoDC maturation/co-stimulatory phenotype between HD and CIR examining CD40, CD70, CD83, CD86, CD137, OX40L, or HLA-DR. No significant differences were observed in MoDC expansion of AFP, GPC3 or CEF-specific IFNγ+ T-cells by Elispot or ICCS. Conclusion: MoDCs isolated from cirrhotic individuals retain similar capacity for activation, maturation and antigen-presentation as those from healthy donors.