Journal Article

CTLA4+CD4+CXCR5−FOXP3+ T cells associate with unfavorable outcome in patients with chronic HBV infection

Wang, Yiyue, Dong, Zheyu, Tang, Libo, Zhou, Yang, Yi, Xuan, Zheng, Xinchun, Li, Xiaoyi, Hou, Jinlin, Wen, Chunhua, Ye, Guofu, Li, Yongyin, Ma, Yanchen

2023

Overview

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.

• Publisher: BioMed Central,BioMed Central Ltd,BMC
• Subject: Allergology / Analysis / Antiviral agents / Antiviral therapy / Biomedical and Life Sciences / Biomedicine / Care and treatment / CD4+CXCR5−FOXP3+T cells / CTLA-4 Antigen / CTLA4 / Cytokines and Growth Factors / Diagnosis / Dosage and administration / Forkhead Transcription Factors / Gene expression / Genetic aspects / HBV / Hepatitis B / Hepatitis B virus / Hepatitis B, Chronic - drug therapy / Humans / Immune response / Immunology / Infection / Liver Failure / Medical research / Medicine, Experimental / Patient outcomes / Prognosis / Receptors, CXCR5 / RNA sequencing / T cells / T-Lymphocytes / Unfavorable outcome / Vaccine