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

Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research
Helen CooksleyShilpa Chokshi

Abstract

Virus-specific T cells are critical in mediating the pathogenesis of hepatitis B virus (HBV) infection. Interferon gamma (IFNγ)-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...Continue Reading

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Citations

Jan 25, 2019·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Na HuangZongfang Li
Sep 25, 2020·Viruses·Huiming CaiQinchang Zhu
May 28, 2021·Journal of Hepatology·Schalk Van der MerweAgustin Albillos

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Methods Mentioned

BETA
flow cytometry
ELISAs

Software Mentioned

BD FACSDiva

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