Priming of HIV-1-specific CD8+ T cells with strong functional properties from naive 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 naive 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 naive cells. Methods: HIV-1-specific CD8(+) T cells were primed from naive 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 naive cells via a strong type I IFN production and suggests that this STING ligand may be useful for AIDS vaccine and cure treatment. (C) 2019 The Authors. Published by Elsevier B.V.