Cytotoxic CD16+γδ T Cells Are Associated with Virus Control in Chronic Hepatitis B Virus (HBV) Infection by Mediating Antibody-Dependent Cellular Cytotoxicity (ADCC)

The role of the immune system in the pathogenesis of HBV infection and the correlates of functional cure are not fully understood. Antibody-dependent cellular cytotoxicity (ADCC) is a possible important mechanism for controlling viral replication. However, its role in CHB, especially the involvement of NK and γδ T cells, which are abundant in the liver, is still unclear.

This study analyzed peripheral NK and γδ T cells in individuals with acute (n=13) and chronic HBV (n=57) using spectral flow cytometry and single-cell RNA sequencing, alongside HBV viral markers. To assess NK and γδ T cell-mediated ADCC, isolated NK or γδ T cells from HBV patients and cord blood were stimulated with HBsAg and intravenous immunoglobulin (IVIG).

We showed that CD16+γδ T cells but not CD16+NK cells negatively correlate with HBcrAg, a marker of intrahepatic HBV replication in CHB. These cells expressed higher levels of cytotoxic markers (granzyme B, perforin, NKG2D), and their stimulation with HBsAg and IVIG led to increased IFN-γ, TNF-α, and CD107a expression. Ex vivo staining of CD16+γδ T cells positively correlated with ADCC in individuals with CHB and acute HBV, while γδ T cells from cord blood, with low CD16 expression, lacked ADCC function.

In conclusion, our results emphasize the role of CD16+γδ T cells and ADCC in the control of HBV during chronic infection. The absence or low levels of CD16+γδ T cell-associated ADCC in cord blood may explain the high rate of CHB in the context of vertical transmission.

Publication History

Article published online:
20 January 2025