Pegylated Interferon α-2a Triggers NK-Cell Functionality and Specific T-Cell Responses in Patients with Chronic HBV Infection without HBsAg Seroconversion

• Published in: PloS one 2016, Vol.11 (6), p.e0158297-e0158297
• Main Authors: Bruder Costa, Juliana, Dufeu-Duchesne, Tania, Leroy, Vincent, Bertucci, Inga, Bouvier-Alias, Magali, Pouget, Noelle, Brevot-Lutton, Ophelie, Bourliere, Marc, Zoulim, Fabien, Plumas, Joel, Aspord, Caroline
• Format: Article
• Language: English
• Subjects: Activation; Adaptive control; Adaptive immunity; Adult; Aged; Antigens; Antiviral drugs; Biology and Life Sciences; Biomarkers; Cancer; CD4 antigen; CD8 antigen; Chronic infection; Cytokines; Cytotoxicity; Dendritic cells; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - metabolism; DNA, Viral; Female; Gastroenterology; Helper cells; Hepatitis; Hepatitis B; Hepatitis B e antigen; Hepatitis B surface antigen; Hepatitis B Surface Antigens - blood; Hepatitis B Surface Antigens - immunology; Hepatitis B, Chronic - blood; Hepatitis B, Chronic - drug therapy; Hepatitis B, Chronic - immunology; Hepatitis B, Chronic - virology; Hepatology; Human health and pathology; Humans; Hépatology and Gastroenterology; Immune response; Immunity; Immunology; Immunotherapy; Infections; Interferon; Interferon-alpha - pharmacology; Interferon-alpha - therapeutic use; Killer Cells, Natural - drug effects; Killer Cells, Natural - immunology; Killer Cells, Natural - metabolism; Laboratories; Life Sciences; Liver Function Tests; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Male; Medicine and Health Sciences; Middle Aged; Natural killer cells; Patients; Phenotype; Polyethylene Glycols - pharmacology; Polyethylene Glycols - therapeutic use; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Research and Analysis Methods; Seroconversion; T cell receptors; T-Cell Antigen Receptor Specificity - immunology; T-Lymphocyte Subsets - drug effects; T-Lymphocyte Subsets - immunology; T-Lymphocyte Subsets - metabolism; T-Lymphocytes - drug effects; T-Lymphocytes - immunology; T-Lymphocytes - metabolism; Therapy; Treatment Outcome; Viral infections; Viral Load; Viruses; α-Interferon
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0158297

Pegylated interferon α-2a (Peg-IFN-α) represents a therapeutic alternative to the prolonged use of nucleos(t)ide analog (NA) in chronic hepatitis B (CHB) infection. The mechanisms leading to a positive clinical outcome remain unclear. As immune responses are critical for virus control, we investigated the effects of Peg-IFN-α on both innate and adaptive immunity, and related it to the clinical evolution. The phenotypic and functional features of the dendritic cells (DCs), natural killer (NK) cells and HBV-specific CD4/CD8 T cells were analyzed in HBeAg-negative CHB patients treated for 48-weeks with NA alone or together with Peg-IFN-α, before, during and up to 2-years after therapy. Peg-IFN-α induced an early activation of DCs, a potent expansion of the CD56bright NK subset, and enhanced the activation and functionality of the CD56dim NK subset. Peg-IFN-α triggered an increase in the frequencies of Th1- and Th17-oriented HBV-specific CD4/CD8 T cells. Peg-IFN-α reversed the unresponsiveness of patients to a specific stimulation. Most of the parameters returned to baseline after the stop of Peg-IFN-α therapy. Peg-IFN-α impacts both innate and adaptive immunity, overcoming dysfunctional immune responses in CHB patients. These modulations were not associated with seroconversion, which questioned the benefit of the add-on Peg-IFN-α treatment.