Imprint of unconventional T-cell response in acute hepatitis C persists despite successful early antiviral treatment.

Autor: Du Y; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany., Khera T; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Strunz B; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Deterding K; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Todt D; Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany.; European Virus Bioinformatics Center (EVBC), Jena, Germany., Woller N; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Engelskircher SA; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Hardtke S; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.; German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany., Port K; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Ponzetta A; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Steinmann E; Department of Molecular and Medical Virology, Ruhr University Bochum, Bochum, Germany., Cornberg M; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.; German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany.; Center for Individualized Infection Medicine (CIIM), Hannover, Germany.; Twincore, Centre for Experimental and Clinical Infection Research, Hannover, Germany.; Cluster of Excellence Resolving Infection Susceptibility (RESIST: EXC), Hannover Medical School, Hannover, Germany., Hengst J; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany., Björkström NK; Center for Infectious Medicine, Department of Medicine Huddinge, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden., Wedemeyer H; Department of Gastroenterology and Hepatology, University Hospital Essen, University of Duisburg-Essen, Essen, Germany.; Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany.; German Center for Infection Research (DZIF), HepNet Study-House, Hannover, Germany.
Jazyk: angličtina
Zdroj: European journal of immunology [Eur J Immunol] 2022 Mar; Vol. 52 (3), pp. 472-483. Date of Electronic Publication: 2021 Dec 13.
DOI: 10.1002/eji.202149457
Abstrakt: Unconventional T cells (UTCs) are a heterogeneous group of T cells that typically exhibit rapid responses toward specific antigens from pathogens. Chronic hepatitis C virus (HCV) infection causes dysfunction of several subsets of UTCs. This altered phenotype and function of UTCs can persist over time even after direct-acting antiviral (DAA)-mediated clearance of chronic HCV. However, it is less clear if and how UTCs respond in acute, symptomatic HCV infection, a rare clinical condition, and if rapid DAA treatment of such patients reverses the caused perturbations within UTCs. Here, we comprehensively analyzed the phenotype and reinvigoration capacity of three major UTC populations, mucosal-associated invariant T (MAIT) cells, γδ T cells, and CD4 and CD8 double-negative αβ T cells (DNT cells) before, during, and after DAA-mediated clearance of acute symptomatic HCV infection. Furthermore, MAIT cell functionality was systematically studied. We observed a reduced frequency of MAIT cells. However, remaining cells presented with a near-to-normal phenotype in acute infection, which contrasted with a significant dysfunction upon stimulation that was not restored after viral clearance. Notably, DNT and γδ T cells displayed a strong activation ex-vivo in acute HCV infection, which subsequently normalized during the treatment. In addition, DNT cell activation was specifically associated with liver inflammation and inflammatory cytokines. Altogether, these data provide evidence that UTCs respond in a cell type-specific manner during symptomatic HCV infection. However, even if early treatment is initiated, long-lasting imprints within UTCs remain over time.
(© 2021 The Authors. European Journal of Immunology published by Wiley-VCH GmbH.)
Databáze: MEDLINE
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