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.

Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro / Rossi, Marzia; Vecchi, Andrea; Tiezzi, Camilla; Barili, Valeria; Fisicaro, Paola; Penna, Amalia; Montali, Ilaria; Daffis, Stephane; Fletcher, Simon P; Gaggar, Anuj; Medley, Jonathan; Graupe, Michael; Lad, Latesh; Loglio, Alessandro; Soffredini, Roberta; Borghi, Marta; Pollicino, Teresa; Musolino, Cristina; Alfieri, Arianna; Brillo, Federica; Laccabue, Diletta; Massari, Marco; Boarini, Chiara; Abbati, Gianluca; Pedrazzi, Giuseppe; Missale, Gabriele; Lampertico, Pietro; Ferrari, Carlo; Boni, Carolina. - In: GUT. - ISSN 0017-5749. - (2023). [10.1136/gutjnl-2022-327202]

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

Rossi, Marzia;Tiezzi, Camilla;Barili, Valeria;Montali, Ilaria;Laccabue, Diletta;Pedrazzi, Giuseppe;Missale, Gabriele;Ferrari, Carlo
;
Boni, Carolina
2023-01-01

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.
2023
Phenotypic CD8 T cell profiling in chronic hepatitis B to predict HBV-specific CD8 T cell susceptibility to functional restoration in vitro / Rossi, Marzia; Vecchi, Andrea; Tiezzi, Camilla; Barili, Valeria; Fisicaro, Paola; Penna, Amalia; Montali, Ilaria; Daffis, Stephane; Fletcher, Simon P; Gaggar, Anuj; Medley, Jonathan; Graupe, Michael; Lad, Latesh; Loglio, Alessandro; Soffredini, Roberta; Borghi, Marta; Pollicino, Teresa; Musolino, Cristina; Alfieri, Arianna; Brillo, Federica; Laccabue, Diletta; Massari, Marco; Boarini, Chiara; Abbati, Gianluca; Pedrazzi, Giuseppe; Missale, Gabriele; Lampertico, Pietro; Ferrari, Carlo; Boni, Carolina. - In: GUT. - ISSN 0017-5749. - (2023). [10.1136/gutjnl-2022-327202]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11381/2948832
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