Acute Exacerbations of Chronic Hepatitis BAre Accompanied by Decline of Core Antigen-Specific Regulatory T-Cell Frequencies: Implications for Successful Anti-HBV Treatments

Background and aims: acute exacerbations (aes) of perinatally-acquired chronic hepatitis b (chb) are accompanied byincreased t cell responses to hepatitis b core and e antigens (hbcag & hbeag). naturally-arising forkhead transcriptionfactor foxp3 (forkhead box p3)-expressing cd4+cd2s+ regulatory t (treg ) cells are thought to be important in thecontrol of infectious diseases. this study aimed to investigate whether hbcag-specific treg cells playa role in modulatingspontaneous aes and in influencing the outcome of anti-hepatitis b virus (hbv) treatments.methods: the syfpeithi scoring system was employed to predict epitope peptides on hbcag overlapping with hbeagfor the construction of peptide-hla class ii tetramers to measure hbcag-specific treg cell frequencies (treg f).results: hbcag-specific treg fdeclined significantly in association with increased hbcag-specific cytotoxic t lymphocytefrequencies during spontaneous aes without treatment. vigorous in vitro expansion of cd4+cd2s+ treg cells from chbpatients responding to hbcag and/or its peptides plus interleukin-2 (il-2) was consistently detected. depletion of tregcells from peripheral blood mononuclear cells enhanced proliferation to hbcag. in contrast, patients with aes whoreceived anti-hbv treatments with oral nucleoside analogues or interferon-alpha injection revealed that more posttreatmentincrease of hbcag-specific treg f correlated with a higher sustained remission rate to the therapy.conclusions: these data indicate that hbcag-specific treg cells from perinatally-acquired chb patients are proliferativeto hbcag and its peptides and exhibit suppressor activity. they playa crucial role in modulating spontaneous aes andin successful anti-hbv treatments.