Priming of HIV-1-specific CD8(+) T cells with strong functional properties from naïve T cells

BACKGROUND: HIV-1-specific CD8(+) T cells are required for immune suppression of HIV-1 replication and elimination of the associated viral reservoirs. However, effective induction of functional HIV-1-specific CD8(+) T cells from naïve cells remains problematic in the setting of human vaccine trials. In this study, we investigated priming of functional HIV-1-specific CD8(+) T cells from naïve cells. METHODS: HIV-1-specific CD8(+) T cells were primed from naïve T cells of HIV-1-seronegative individuals using TLR4 ligand LPS or STING ligand 3′3′-cGAMP in vitro. We established HIV-1-specific CD8(+) T cell lines from primed T cells and then investigated functional properties of these cells. FINDINGS: HIV-1-specific CD8(+) T cells primed with LPS failed to suppress HIV-1. In contrast, 3′3′-cGAMP effectively primed HIV-1-specific CD8(+) T cells with strong ability to suppress HIV-1. 3′3′-cGAMP-primed T cells had higher expression levels of perforin and granzyme B than LPS-primed ones. The expression levels of granzyme B and perforin and viral suppression ability of 3′3′-cGAMP-primed T cells were positively correlated with the production level of type I IFN from PBMCs stimulated with 3′3′-cGAMP. INTERPRETATION: The present study demonstrates the potential of 3′3′-cGAMP to induce HIV-1-specific CD8(+) T cells with strong effector function from naïve cells via a strong type I IFN production and suggests that this STING ligand may be useful for AIDS vaccine and cure treatment.