Restoration of HBV-specific CD8+T-cell responses by sequential low-dose IL-2 treatment in non-responder patients after IFN-αtherapy  

作　　者：Dongyao Wang Binqing Fu Xiaokun Shen Chuang Guo Yanyan Liu Junfei Zhang Rui Sun Ying Ye Jiabin Li Zhigang Tian Haiming Wei 

机构地区：[1]Institute of Immunology and the CAS Key Laboratory of Innate Immunity and Chronic Disease,School of Basic Medicine and Medical Center,University of Science and Technology of China,Hefei,Anhui 230001,China [2]Hefei National Laboratory for Physical Sciences at Microscale,University of Science and Technology of China,Hefei,Anhui 230001,China [3]Department of Infectious Diseases,the First Affiliated Hospital of Anhui Medical University,Hefei,Anhui 230027,China

出　　处：《Signal Transduction and Targeted Therapy》2021年第12期3684-3696,共13页信号转导与靶向治疗（英文）

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).

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.

关 键 词：PATIENTS TREATMENT RESTORATION 

分 类 号：R512.62[医药卫生—内科学]