Mucosal-associated invariant T (MAIT) cells exert direct anti-viral effector function against HBV

Chronic infection with hepatitis B virus (CHB) represents a major global health burden affecting more than 250 million people worldwide. Conventional virus-specific CD8+T cells can clear hepatitis B virus (HBV), but often become dysfunctional in CHB. Here, we aimed to determine whether mucosal-associated invariant T (MAIT) cells, innate like T cells enriched in the liver, possess anti-viral effector function against HBV.

Primary human MAIT cells isolated from peripheral blood of CHB patients with or without nucleos(t)ide analogue (NUC) treatment or controls were activated and co-cultured with HepG2-NTCP cells infected with HBV. MAIT cell cytokine expression, HBe-antigen and cccDNA were quantified by ELISA and qPCR. MAIT cell cytotoxicity was tested by real-time viability assay using xCelligence.

Following ex vivo activation, MAIT cells killed HBV-infected HepG2-NTCP cells and limited HBV replication in HepG2-NTCP cells, indicating a direct anti-viral effector function of MAIT cells against HBV. Notably, MAIT cell anti-viral effector function required T cell receptor-mediated stimulation. Employing a transwell system revealed that MAIT cells limit HBV replication in a cell-contact independent, cytokine-mediated manner. Importantly, MAIT cells from patients with CHB without NUC treatment expressed markedly lower levels of the effector cytokines IFNy and TNFa and lost their capacity to limit HBV replication.

Our data uncover a direct antiviral effector function of innate-like MAIT cells against HBV that is impaired in patients with CHB and could be targeted to improve the anti-viral immune response against HBV.

Publication History

Article published online:
20 January 2025