Changes of Costimulatory Molecule CD28 on Circulating CD8(+) T Cells Correlate with Disease Pathogenesis of Chronic Hepatitis B

Costimulatory signals are critical for antiviral immunity. The aim of this study was to evaluate the change of costimulatory molecule CD28 on circulating CD8(+) T cells in chronic hepatitis B patients (CHB). Seventy CHB patients and fifty-six healthy controls were included, and forty-eight CHB patients were recruited for 52 weeks of longitudinal investigation. The proportions of circulating CD8(+)CD28(+) and CD8(+)CD28(−) subpopulations were determined by flow cytometry, and the CD8(+)CD28(+)/CD8(+)CD28(−) T cells ratio was calculated. Compared with the subpopulation in healthy controls, high proportions of CD8(+)CD28(−) subpopulation were observed in CHB patients. Similarly, the CD8(+)CD28(+)/CD8(+)CD28(−) T cells ratio was significantly decreased in CHB patients compared with healthy controls and correlated significantly with hepatitis B virus (HBV) loads. High proportions of CD8(+)CD28(−) subpopulation and low CD8(+)CD28(+)/CD8(+)CD28(−) T cells ratio were observed in hepatitis B e antigen- (HBeAg-) positive individuals as compared with that in HBeAg-negative subjects. A significant decrease in CD8(+)CD28(−) subpopulation, increase in CD8(+)CD28(+) subpopulation, and CD8(+)CD28(+)/CD8(+)CD28(−) T cells ratio were seen in those patients who received efficient antiviral therapy. Thus, aberrant CD28 expression on circulating CD8(+) T cells and the CD8(+)CD28(+)/CD8(+)CD28(−) T cells ratio reflect the dysregulation of T cell activation and are related to the pathogenesis of chronic HBV infection.