Serum vitamin D deficiency is associated with increased risk of γδ T cell exhaustion in HBV-infected patients.

Previous studies have demonstrated that T cell exhaustion is associated with poor clearance of Hepatitis B virus (HBV). However, whether the expression of exhaustion markers on innate-like circulating γδ T cells derived from patients with HBV infection correlates with the serum level of vitamin D is not completely understood. In this study, we found that the frequency of circulating Vδ2+ T cell and serum levels of vitamin 25(OH)D3 were significantly decreased in patients with HBV. And serum 25(OH)D3 levels in HBV-infected patients were negatively correlated with HBV DNA load and PD-1 expression on γδ T cells. Interestingly, 1α,25(OH)2 D3 alleviated the exhaustion phenotype of Vδ2 T cells in HBV-infected patients and promoted IFN-β expression in human cytotoxic Vδ2 T cells in vitro. Collectively, these findings demonstrate that vitamin D plays a pivotal role in reversing γδ T-cell exhaustion and is highly promising target for ameliorating HBV infection.