Exhaustion of CD8+ T Cells in HBV Infection: Searching for Serological Markers.

Abstract

Objective: Chronic infection of the hepatitis B virus (HBV) is associated with the dysfunction and exhaustion of CD8+ T cells, which are crucial in controlling HBV. While clinical parameters provide insight into the state of HBV infection, the relationship between HBV biochemical parameters and CD8+ T cell exhaustion remains poorly understood. This study aimed to evaluate the expression of activation, exhaustion, and function-related markers in CD8+ T cells of HBV carriers, and to determine the potential of HBV clinical parameters as biomarkers for CD8+ T cell exhaustion.

Methods: We enrolled 93 patients with HBV and measured the expression levels of CD160, T cell Ig and mucin-domain containing-3 (Tim-3), programmed cell death protein 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), CD28, CD137, granzyme B, and perforin in CD8+ T cells using flow cytometry. HBV clinical parameters including, HBsAg, HBsAb, HBeAg, HBeAb, HBcAb, HBV DNA load, ALT, AST, ABil, and ALB, were measured in the blood samples.

Results: Patients were divided into two groups, HBV DNA+, and HBV DNA-, based on whether their HBV DNA load was below the test baseline; ALT, AST, and CD160+CD8+ T cell percentages were significantly higher in the HBV DNA+ group than in the HBV DNA- group (P=0.0323; P=0.0072; P=0.0458). However, the granzyme B-expressing CD8+ T cell percentage in the HBV DNA-group was higher than the HBV DNA+ group (P=0.0497). In the HBV DNA+ group, CD160, Tim-3, CD28, and perforin were significantly correlated with ALT, granzyme B was significantly correlated with AST; however, there was no correlation with HBV DNA load.

Conclusion: It is possible to infer the level of CD8+ T cell exhaustion in patients with an HBV DNA load >10² copies/mL based on clinical parameters (such as ALT, AST, and ABIL).