摘要
Patients with chronic hepatitis B(CHB)undergoing interferon(IFN)-α-based therapies often exhibit a poor HBeAg serological response.Thus,there is an unmet need for new therapies aimed at CHB.This study comprised two clinical trials,including 130 CHB patients,who were treatment-naïve;in the first,92 patients were systematically analyzed ex vivo for interleukin-2 receptor(IL-2R)expression and inhibitory molecules expression after receiving Peg-IFN-α-2b therapy.In our second clinical trial,38 non-responder patients,in whom IFN-αtherapy had failed,were treated with or without low-dose IL-2 for 24 weeks.We then examined the hepatitis B virus(HBV)-specific CD8+T-cell response and the clinical outcome,in these patients.Although the majority of the participants undergoing Peg-IFN-α-2b therapy were non-responders,we observed a decrease in CD25 expression on their CD4+T cells,suggesting that IFN-αtherapy may provide a rationale for sequential IL-2 treatment without increasing regulatory T cells(Tregs).Following sequential therapy with IL-2,we demonstrated that the non-responders experienced a decrease in the numbers of Tregs and programmed cell death protein 1(PD-1)expression.In addition,sequential IL-2 administration rescued effective immune function,involving signal transducer and activator of transcription 1(STAT1)activation.Importantly,IL-2 therapy significantly increased the frequency and function of HBV-specific CD8+T cells,which translated into improved clinical outcomes,including HBeAg seroconversion,among the non-responder CHB patients.Our findings suggest that sequential IL-2 therapy shows efficacy in rescuing immune function in non-responder patients with refractory CHB.
基金
This work was supported by the Natural Science Foundation of China(Nos.81330071,31390433 and 81922028)
the Fundamental Research Funds for the Central Universities(WK9110000168)
the Youth Innovation Promotion Association of Chinese Academy of Sciences(No.2019442).
