Differential Expression of Immune Inhibitory Checkpoint Signatures on Antiviral and Inflammatory T Cell Populations in Chronic Hepatitis B
| Autor: | H. Cooksley, K. Katzarov, Roger Williams, Marieta Simonova, Shilpa Chokshi, Antonio Riva, S. Pavlova, Tanya Hadzhiolova-Lebeau |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Adult CD4-Positive T-Lymphocytes Male T cell Immunology Inflammation CD8-Positive T-Lymphocytes medicine.disease_cause Proinflammatory cytokine 03 medical and health sciences Interferon-gamma Immune system Hepatitis B Chronic Virology Medicine Humans Interferon gamma Receptor Cells Cultured Hepatitis B virus biology business.industry Interleukin-17 Cell Biology Middle Aged 030104 developmental biology medicine.anatomical_structure biology.protein Female medicine.symptom Antibody business medicine.drug |
| Zdroj: | Journal of interferoncytokine research : the official journal of the International Society for Interferon and Cytokine Research. 38(7) |
| ISSN: | 1557-7465 |
| Popis: | 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 IFNγ 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 IFNγ responses without affecting inflammatory IL-17 production. |
| Databáze: | OpenAIRE |
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