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

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

来源：BMC IMMUNOLOGY, 2023, 24(1): 3.

DOI：10.1186/s12865-022-00537-w

• HBV
• Antiviral therapy
• Unfavorable outcome
• CD4(+)CXCR5(-)FOXP3(+)T cells
• CTLA4

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-naive 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-naive 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.

• 单位
  南方医科大学; 5; 中山大学