Pegylated interferon α-2a triggers NK-cell functionality and specific T-cell responses in patients with chronic HBV infection without HBsAg seroconversion
| Autor: | Ophelie Brevot-Lutton, Noelle Pouget, Tania Dufeu-Duchesne, Caroline Aspord, Magali Bouvier-Alias, Joel Plumas, Marc Bourlière, Juliana Bruder Costa, Vincent Leroy, Inga Bertucci, Fabien Zoulim |
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| Přispěvatelé: | Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble) (IAB), Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service d'Hépato-gastroentérologie, Assistance Publique - Hôpitaux de Marseille (APHM), Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Institut de biologie et chimie des protéines [Lyon] (IBCP), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), ANRS, Agence Nationale de Recherches sur le Sida et les Hepatites Virales, Centre Hospitalier Universitaire [Grenoble] (CHU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Etablissement français du sang - Auvergne-Rhône-Alpes (EFS)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon |
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Male
T-Cell Antigen Receptor Specificity Lymphocyte Activation Polyethylene Glycols Interleukin 21 0302 clinical medicine Animal Cells T-Lymphocyte Subsets phase 3 clinical trial (topic) T lymphocyte Public and Occupational Health IL-2 receptor CD8+ T lymphocyte lcsh:Science Immune Response Innate Immune System clinical article Innate lymphoid cell Acquired immune system 3. Good health cell activation Killer Cells Natural lymphocyte function Interleukin 12 Cytokines 030211 gastroenterology & hepatology Cellular Types phenotype Immune Cells T cell Immunology Cytotoxic T cells Article peginterferon alpha2a 03 medical and health sciences Hepatitis B Chronic Humans chronic hepatitis B T Helper Cells human seroconversion Aged CD4+ T lymphocyte Blood Cells Hepatitis B Surface Antigens human cell lcsh:R Biology and Life Sciences Dendritic Cells Molecular Development hepatitis B surface antigen 030104 developmental biology DNA Viral lcsh:Q Preventive Medicine Biomarkers Developmental Biology 0301 basic medicine Physiology T-Lymphocytes lcsh:Medicine NK cells White Blood Cells Liver Function Tests Immune Physiology Medicine and Health Sciences randomized controlled trial (topic) innate immunity Staining Multidisciplinary T Cells Cell Staining adaptive immunity Middle Aged Viral Load Vaccination and Immunization Recombinant Proteins Treatment Outcome medicine.anatomical_structure multicenter study (topic) Female Research Article Adult dendritic cell [SDV.CAN]Life Sciences [q-bio]/Cancer cellular immunity Biology Research and Analysis Methods Natural killer cell Immune system Antiviral Therapy evolution medicine drug mechanism controlled study nucleoside analog Interferon-alpha [SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology Cell Biology natural killer cell Specimen Preparation and Treatment Immune System |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2016, 11 (6), pp.e0158297. ⟨10.1371/journal.pone.0158297⟩ PLoS ONE, 2016, 11 (6), pp.e0158297. ⟨10.1371/journal.pone.0158297⟩ PLoS ONE, Vol 11, Iss 6, p e0158297 (2016) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0158297⟩ |
| Popis: | International audience; 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. © 2016 Bruder Costa et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
| Databáze: | OpenAIRE |
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