Mechanism of restoration of immune responses of patients with chronic hepatitis B during lamivudine therapy: increased antigen processing and presentation by dendritic cells

Abstract

Restoration of host immunity has been reported in patients with chronic hepatitis B (CHB) after treatment with lamivudine; however, the underlying mechanisms of this treatment have not been determined. This study examined the role of antigen-presenting dendritic cells (DC) in restoration of host immunity. Circulating DC were isolated from peripheral blood of 23 patients with CHB before and 1, 3, and 12 months after starting lamivudine therapy. The non-antigen-specific proliferation of DC was assessed in allogenic mixed leucocyte reaction. Dendritic cells were cultured with hepatitis B surface antigen (HBsAg) to prepare HBsAg-pulsed DC. Proliferative capacity and production of interleukin (IL)-12 and interferon (IFN)-γ of HBsAg-pulsed DC were evaluated. Circulating unpulsed DC and HBsAg-pulsed DC showed significantly higher levels of T-cell proliferation capacities 1 month after lamivudine therapy compared to proliferation levels before therapy (P<0.05). HBsAg-pulsed DC also produced significantly higher levels of IL-12 and IFN-γ with lamivudine therapy compared to levels before therapy (P<0.05). HBsAg-pulsed DC from lamivudine-treated patients induced proliferation of T cells of patients with CHB in an antigen-specific manner (P<0.05). However, T-cell stimulatory capacity of DC did not increase significantly 3 and 12 months after lamivudine therapy compared to 1 month after lamivudine therapy. Immune restoration as a result of lamivudine therapy is regulated at least in part by activation of DC. However, progressive activation of DC was not seen as treatment duration progressed, indicating the limitations of this mechanism of viral clearance.

Telbivudine therapy may shape CD4+ T‐cell response to prevent liver fibrosis in patients with chronic hepatitis B

“…Without direct effects on host immunity, NAs could effectively disturb the replication circles of HBV to decrease the viral antigen load, which is also beneficial for the reconstruction of antiviral immunity. Thus, several researches have suggested that early immune restoration during NAs therapy could partly reflect and even predict the long‐term therapeutic responses . Here, for the first time, we made a thorough analysis of four CD4 + T subsets in both the cross‐sectional and longitudinal studies during chronic HBV infection, and designed several in vitro experiments to investigate the effects of reconstructed CD4 + T cells on the profibrogenic features of HSCs, which might be informative in understanding the roles of CD4 + T‐cell responses in both the host–virus interactions and the inflammation–fibrosis cross‐talks.…”

Hepatitis B Surface Antigen Could Contribute to the Immunopathogenesis of Hepatitis B Virus Infection

“…However, vaccines consisting of recombinant HBsAg and anti-HBs immunoglobulins could induce HBs-specific T cells efficiently since the formation of Ag-Ab immune complexes could be easily captured and taken up by DCs [96]. Although HBsAg might suppress the functions of DCs [11], HBsAg-pulsed DCs might enhance HBV-specific immune response in CHB patients [97]. …”

Immunopathogenesis and prognostic immune markers of chronic hepatitis B virus infection

“…Similarly, the recovery of functional pDCs during IFN‐α therapy may also have the same predictive value 48 . A recent study further reported that lamivudine therapy is able to reduce HBV DNA to an undetectable level, but the patients may only exhibit a transient restoration of circulating DC 49 . These findings suggest that the dynamics of DC frequency and functionality are associated with the responsiveness to antiviral therapy in CHB patients, and thus have the potential to serve as prognostic markers for HBV disease progression and treatment efficacy.…”