Hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells from HBV-associated hepatocellular carcinoma patients significantly enhance specific T cell responses in vitro
Open Access
- 21 December 2006
- journal article
- Published by Oxford University Press (OUP) in Clinical and Experimental Immunology
- Vol. 147 (2), 277-286
- https://doi.org/10.1111/j.1365-2249.2006.03281.x
Abstract
To investigate whether hepatitis B virus (HBV) antigen-pulsed monocyte-derived dendritic cells (MoDC) could mount a T cell response in hepatocellular carcinoma (HCC) patients associated with chronic HBV infection, peripheral blood mononuclear cells (PBMCs) from 36 HBV-associated HCC patients were induced into MoDC and pulsed with hepatitis B core antigen (HBcAg) and hepatitis B surface antigen (HBsAg), alone and in combination. Co-stimulatory molecules CD80, CD86 and CD40, as well as human leucocyte antigens D-related (HLA-DR) were found to express at the highest level on MoDC pulsed with HBcAg or HBsAg + HBcAg, at a median level on MoDC pulsed with HBcAg or HBsAg alone, and at the lowest level on non-antigen-pulsed MoDC. Interleukin (IL)-10 and IL-12 cytokines were released by antigen-pulsed MoDC at increased levels in the order: no-antigen < HBsAg < HBcAg < HBcAg + HBsAg. MoDC pulsed with HBcAg or HBsAg + HBcAg also had the strongest ability to stimulate autologous T cell proliferation and intracellular interferon (IFN)-γ production. HBcAg- or HBsAg + HBcAg-pulsed MoDC could also induce HBV core peptide-specific CD8+ T cell proliferation determined by tetramer staining. In addition, the antigen-pulsed MoDC were found to have a stronger capacity to produce IL-12 and induce T cell response in vitro for patients with higher alanine transaminase (ALT) levels than those with lower ALT levels, indicating that antigen pulse could substantially reverse the impaired function of MoDC in primary HCC patients with active chronic hepatitis B. In conclusion, HBV antigen-pulsed MoDC from HCC patients with chronic hepatitis B could induce HBV-specific T cell response in vitro.Keywords
This publication has 46 references indexed in Scilit:
- Decreased numbers and impaired function of circulating dendritic cell subsets in patients with chronic hepatitis B infection (R2)Journal of Gastroenterology and Hepatology, 2005
- Phenotype and function of monocyte derived dendritic cells in chronic hepatitis B virus infectionJournal of General Virology, 2004
- Safety and efficacy of hepatitis B surface antigen-pulsed dendritic cells in human volunteersHepatology Research, 2004
- Frequencies of interferon-γ and interleukin-10 secreting cells in peripheral blood mononuclear cells and liver infiltrating lymphocytes in chronic hepatitis B virus infectionHepatology Research, 2003
- Hepatitis B virus‐induced defect of monocyte‐derived dendritic cells leads to impaired T helper type 1 response in vitro: mechanisms for viral immune escapeImmunology, 2003
- Immunogenicity and Tolerogenicity of Hepatitis B Virus Structural and Nonstructural Proteins: Implications for Immunotherapy of Persistent Viral InfectionsJournal of Virology, 2002
- Escaping High Viral Load ExhaustionThe Journal of Experimental Medicine, 2002
- Mechanism and therapeutic potential of DNA-based immunization against the envelope proteins of hepatitis B virus in normal and transgenic miceImmunology, 2001
- Suppression of human hepatoma in mice through adoptive transfer of immunity to the hepatitis B surface antigenJournal of Hepatology, 1997
- Infection of dendritic cells with HIV1: virus load regulates stimulation and suppression of T-cell activityResearch in Virology, 1993