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Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro

Authors :
Marzia Rossi
Andrea Vecchi
Camilla Tiezzi
Valeria Barili
Paola Fisicaro
Amalia Penna
Ilaria Montali
Stephane Daffis
Simon P Fletcher
Anuj Gaggar
Jonathan Medley
Michael Graupe
Latesh Lad
Alessandro Loglio
Roberta Soffredini
Marta Borghi
Teresa Pollicino
Cristina Musolino
Arianna Alfieri
Federica Brillo
Diletta Laccabue
Marco Massari
Chiara Boarini
Gianluca Abbati
Giuseppe Pedrazzi
Gabriele Missale
Pietro Lampertico
Carlo Ferrari
Carolina Boni
Source :
Gut. :gutjnl-2022
Publication Year :
2023
Publisher :
BMJ, 2023.

Abstract

ObjectiveExhausted hepatitis B virus (HBV)-specific CD8 T cells in chronic HBV infection are broadly heterogeneous. Characterisation of their functional impairment may allow to distinguish patients with different capacity to control infection and reconstitute antiviral function.DesignHBV dextramer+CD8 T cells were analysed ex vivo for coexpression of checkpoint/differentiation markers, transcription factors and cytokines in 35 patients with HLA-A2+chronic hepatitis B (CHB) and in 29 control HBsAg negative CHB patients who seroconverted after NUC treatment or spontaneously. Cytokine production was also evaluated in HBV peptide-stimulated T cell cultures, in the presence or absence of antioxidant, polyphenolic, PD-1/PD-L1 inhibitor and TLR-8 agonist compounds and the effect on HBV-specific responses was further validated on additional 24 HLA-A2 negative CHB patients.ResultsSeverely exhausted HBV-specific CD8 T cell subsets with high expression of inhibitory receptors, such as PD-1, TOX and CD39, were detected only in a subgroup of chronic viraemic patients. Conversely, a large predominance of functionally more efficient HBV-specific CD8 T cell subsets with lower expression of coinhibitory molecules and better response to in vitro immune modulation, typically detected after resolution of infection, was also observed in a proportion of chronic viraemic HBV patients. Importantly, the same subset of patients who responded more efficiently to in vitro immune modulation identified by HBV-specific CD8 T cell analysis were also identified by staining total CD8 T cells with PD-1, TOX, CD127 and Bcl-2.ConclusionsThe possibility to distinguish patient cohorts with different capacity to respond to immune modulatory compounds in vitro by a simple analysis of the phenotypic CD8 T cell exhaustion profile deserves evaluation of its clinical applicability.

Subjects

Subjects :
Gastroenterology

Details

ISSN :
14683288 and 00175749
Database :
OpenAIRE
Journal :
Gut
Accession number :
edsair.doi...........ca9cbc2cb47738426d0d3ff0d755465a
Full Text :
https://doi.org/10.1136/gutjnl-2022-327202