Effects of lamivudine on the function of dendritic cells derived from patients with chronic hepatitis B virus infection

摘要

AIM: To investigate if the nucleoside analogue lamivudine (LAM), a potent inhibitor of HBV replication, could restore the function of dendritic cells derived from patients with chronic hepatitis B (CHB) in an Asian population. METHODS: Dendritic cells (DCs) derived from mononuclearcytes of patients with chronic HBV infection were cultured in the presence of IL-4, granulocyte-macrophage colony-stimulating factors (GM-CSF) and gradient concentrations of LAM (0-2 mmol/L). Cell morphology was observed under light microscopy. Cell surface molecules, including HLA-DR, CD80, CD83, and CD1α, were analyzed with flow cytometry. The concentrations of IL-6 and IL-12 in the supernatant were assayed by ELISA. T cell proliferation was assayed by methyl thiazolyl tetrazolium (MTT). RESULTS: The expression of CD1α on DC treated with 0.5 mmol/L LAM (LAM-DC 0.5 mmol/L) was significantly higher than that of DC untreated with LAM (54.1 ± 4.21 vs 33.57 ± 3.14, P < 0.05), and so was the expression of CD83 (20.24 ± 2.51 vs 12.83 ± 2.12, P < 0.05) as well as the expression of HLA-DR (74.5 ± 5.16 vs 52.8 ± 2.51, P < 0.05). Compared with control group, LAM-DC group (0.5 mmol/L) secreted significantly more IL-12 (910 ± 91.5 vs 268 ± 34.3 pg/mL, P < 0.05), had lower levels of IL-6 in the culture supernatant (28 ± 2.6 vs 55 ± 7.36 pg/mL, P < 0.05), markedly enhanced the stimulatory capacity in the allogeneic mixed leukocyte reaction (MLR) (1.87 ± 0.6 vs 1.24 ± 0.51, P < 0.05).CONCLUSION: The lower expression of phenotypic molecules and impaired allogeneic mixed lymphocyte reaction function of dendritic cells derived from patients with HBV infection could be restored in vitro by incubation with LAM.