Pegylated interferon α-2a triggers NK-cell functionality and specific T-cell responses in patients with chronic HBV infection without HBsAg seroconversion

J.B. Costa (1) , T. Dufeu-Duchesne (1) , V. Leroy (1) , I. Bertucci , M. Bouvier-Alias (2) , N. Pouget (3) , O. Brevot-Lutton (3) , M. Bourlière (4) , F. Zoulim (5, 6) , J. Plumas (1) , C. Aspord (1)

1 IAB - Institute for Advanced Biosciences / Institut pour l'Avancée des Biosciences (Grenoble)
2 IMRB - Institut Mondor de Recherche Biomédicale
3 iPLESP - Institut Pierre Louis d'Epidémiologie et de Santé Publique
4 Service d'Hépato-gastroentérologie
5 UNICANCER/CRCL - Centre de Recherche en Cancérologie de Lyon
6 IBCP - Institut de biologie et chimie des protéines [Lyon]

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.

Mots clés: chronic hepatitis B; clinical article; CD4+ T lymphocyte; Article; dendritic cell; controlled study; drug mechanism; evolution; cellular immunity; cell activation; CD8+ T lymphocyte; human; human cell; peginterferon alpha2a; adaptive immunity; nucleoside analog; hepatitis B surface antigen; lymphocyte function; innate immunity; multicenter study (topic); phase 3 clinical trial (topic); natural killer cell; randomized controlled trial (topic); phenotype; seroconversion; T lymphocyte

Domaines: Cancer; Hépatologie et Gastroentérologie

J.B. Costa, T. Dufeu-Duchesne, V. Leroy, I. Bertucci, M. Bouvier-Alias, et al.. Pegylated interferon α-2a triggers NK-cell functionality and specific T-cell responses in patients with chronic HBV infection without HBsAg seroconversion. PLoS ONE, 2016, 11 (6), pp.e0158297. ⟨10.1371/journal.pone.0158297⟩. ⟨hal-01427005⟩