Immunomodulation Induced During Interferon-α Therapy Impairs the Anti-HBV Immune Response Through CD24 + CD38 hi B Cells

• Published in: Frontiers in immunology Vol. 11; p. 591269
• Main Authors: Fu, Binqing, Wang, Dongyao, Shen, Xiaokun, Guo, Chuang, Liu, Yanyan, Ye, Ying, Sun, Rui, Li, Jiabin, Tian, Zhigang, Wei, Haiming
• Format: Journal Article
• Language: English
• Published: Switzerland 2020
• Subjects: Peg-IFNα-2b; CD24+CD38hi B; immunomodulatory effects; anti-virus function; chronic hepatitis B virus infection
• ISSN: 1664-3224

Type I interferon is widely used for antiviral therapy, yet has yielded disappointing results toward chronic HBV infection. Here we identify that PEG-IFNα-2b therapy toward persistent infection in humans is a double-edged sword of both immunostimulation and immunomodulation. Our studies of this randomised trial showed persistent PEG-IFNα-2b therapy induced large number of CD24 CD38 B cells and launched a CD24 CD38 B cells centered immunosuppressive response, including downregulating functions of T cells and NK cells. Patients with low induced CD24 CD38 B cells have achieved an improved therapeutic effect. Specifically, using the anti-CD24 antibody to deplete CD24 CD38 B cells without harming other B cell subsets suggest a promising strategy to improve the therapeutic effects. Our findings show that PEG-IFNα-2b therapy toward persistent infection constitutes an immunomodulation effect, and strategies to identifying the molecular basis for the antiviral versus immunomodulatory effects of PEG-IFNα-2b to selectively manipulate these opposing activities provide an opportunity to ameliorate anti-virus immunity and control viral infection.