CTLA4+CD4+CXCR5-FOXP3+ T cells associate with unfavorable outcome in patients with chronic HBV infection.
BMC Immunol
; 24(1): 3, 2023 01 12.
Article
em En
| MEDLINE
| ID: mdl-36635631
ABSTRACT
BACKGROUND:
A major barrier to achieving a favorable outcome of chronic HBV infection is a dysregulated HBV-specific immune response resulting from immunosuppressive features of FOXP3+ T cells. A better definition of FOXP3+ T cells is essential for improving the prognosis of HBV infection. We aimed to investigate the role of CD4+CXCR5-FOXP3+ T cells with CTLA4 expression in patients with chronic HBV infection.METHODS:
Treatment-naïve chronic HBV-infected patients, HBV-related hepatic failure, and a longitudinal cohort of chronic hepatitis B (CHB) patients with nucleos(t)ide analogue treatment were enrolled for analysis of CD4+CXCR5-FOXP3+ T cell responses by flow cytometry and single-cell RNA sequencing (scRNA-seq).RESULTS:
ScRNA-seq revealed that circulating CD4+CXCR5-FOXP3+ T cells presented distinct inhibitory features compared to spleen tissue. Meanwhile, patients with treatment-naïve chronic HBV infection or with HBV-related hepatic failure showed an upregulation of immune-suppressive features (PD-1, CTLA4, GITR) on CD4+CXCR5-FOXP3+T cells; in vitro analysis found HBeAg and HBcAg stimulation induced elevated levels of inhibitory molecules. Notably, the frequency of CTLA4+CD4+CXCR5-FOXP3+ T cells was positively correlated with HBV DNA levels, and longitudinal analysis demonstrated a high frequency of this subset at 12 weeks of antiviral treatment predicted unfavorable outcome in CHB patients.CONCLUSIONS:
CTLA4+CD4+CXCR5-FOXP3+ T cells are related to unfavorable outcomes in HBV-infected patients; these data indicated that alleviating CTLA4+CD4+CXCR5-FOXP3+ T cells may improve the prognosis of HBV infection.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Linfócitos T
/
Falência Hepática
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Hepatite B Crônica
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article