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

• Published in: BMC immunology 2023-01, Vol.24 (1), p.3-3, Article 3
• Main Authors: Wen, Chunhua, Dong, Zheyu, Wang, Yiyue, Ye, Guofu, Ma, Yanchen, Yi, Xuan, Zhou, Yang, Li, Xiaoyi, Zheng, Xinchun, Hou, Jinlin, Li, Yongyin, Tang, Libo
• Format: Article
• Language: English
• Subjects: Antiviral therapy; CD4+CXCR5−FOXP3+T cells; CTLA-4 Antigen; CTLA4; Forkhead Transcription Factors; HBV; Hepatitis B virus; Hepatitis B, Chronic - drug therapy; Humans; Liver Failure; Receptors, CXCR5; T-Lymphocytes; Unfavorable outcome
• ISSN: 1471-2172; 1471-2172
• DOI: 10.1186/s12865-022-00537-w

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. 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). 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. 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.