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

Abstract Background HIV-1-specific CD8+ T cellsare 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 cellsfrom naive cells remains problematic in the setting of human vaccine trials. In this study, we investigated priming of functional HIV-1-specific CD8+ T cellsfrom naive cells. Methods HIV-1-specific CD8+ T cellswere primed from naive T cellsof HIV-1-seronegative individuals using TLR4 ligand LPS or STINGligand 3′3′-cGAMP in vitro . We established HIV-1-specific CD8+ T celllines from primed T cellsand then investigated functional properties of these cells. Findings HIV-1-specific CD8+ T cellsprimed with LPS failed to suppress HIV-1. In contrast, 3′3′-cGAMP effectively primed HIV-1-specific CD8+ T cellswith strong ability to suppress HIV-1. 3′3′-cGAMP-primed T cellshad higher expression levels of perforinand granzyme Bthan LPS-primed ones. The expression levels of granzyme Band perforinand viral suppression ability of 3′3′-cGAMP-primed T cellswere 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 cellswith strong effector function from naive cells via a strong type I IFN production and suggests that this STINGligand may be useful for AIDS vaccine and cure treatment.