Differential Expression of Immune Inhibitory Checkpoint Signatures on Antiviral and Inflammatory T Cell Populations in Chronic Hepatitis B

作者：Cooksley Helen; Riva Antonio; Katzarov Krum; Hadzhiolova Lebeau Tanya; Pavlova Slava; Simonova Marieta; Williams Roger; Chokshi Shilpa^*

来源：Journal of Interferon and Cytokine Research, 2018, 38(7): 273-282.

DOI：10.1089/jir.2017.0109

• hepatitis B virus (HBV)
• immune regulation
• interferon gamma (IFN)
• interleukin-17 (IL-17)
• programmed death-1 (PD-1)
• T cell immunoglobulin domain and mucin domain-3 (TIM-3)
• checkpoint receptor inhibition

Virus-specific T cells are critical in mediating the pathogenesis of hepatitis B virus (HBV) infection. Interferon gamma (IFN)-producing T cells are associated with resolution; in contrast, interleukin-17 (IL-17)-producing T cells are linked to exacerbation of liver inflammation and injury. Checkpoint receptors stringently regulate T cell functions, with their expression profiles varying on different T cell subsets. Blockade of checkpoint receptors may be an effective therapeutic strategy for chronic hepatitis B (CHB); however, blockade may also inadvertently exacerbate proinflammatory responses. In this study, we sought to determine the balance of inflammatory and antiviral T cells and determine their inhibitory receptor profile. The frequency of total and HBV antigen-specific Th17 and Tc17 cells was higher in CHB patients compared with healthy controls (HCs). Th17 and Tc17 cells in CHB patients had significantly lower expression of T cell immunoglobulin and mucin domain protein-3 (TIM-3) compared with HCs, with no difference in programmed death-1 (PD-1) or CD244 expression. Conversely, Th1 and Tc1 cells in CHB patients hyperexpressed PD-1 and CD244, while TIM-3 expression was comparable in both cohorts. During CHB, antiviral IFN T cells hyperexpress multiple immune inhibitory receptors driving their functional impairment. In contrast, inflammatory Th17/Tc17 cells hypoexpress TIM-3, but not PD-1 or CD244. Checkpoint inhibitors for CHB should target PD-1 or CD244 to allow restoration of IFN responses without affecting inflammatory IL-17 production.

• 出版日期2018-7
• 单位中国人民解放军军事医学科学院