Inhibition of TIGIT on NK cells improves their cytotoxicity and HIV reservoir eradication potential

As a major barrier to human immunodeficiency virus (HIV) cure, HIV reservoir persist in viremia-suppressed infected individuals. NK cells are important antiviral cells, and their impact on reservoir has rarely been reported. We analyzed the relationship between the size of reservoir and NK cell subsets, inhibitory receptor TIGIT expression. Our analysis found that the percentage of CD56^-CD16⁺ NK cells was positively associated with HIV reservoir size. Furthermore, TIGIT expression on NK cells and CD56^-CD16⁺ NK cells or CD56^dim NK cells has a positive correlation with the HIV reservoir. TIGIT can inhibit the PI3K-Akt-mTOR-mTORC1 (s6k) signaling pathway to decrease the production of IFN-γ on NK cells. Blocking TIGIT in NK cells can enhance their ability to eliminate reactivated latently infected CD4⁺ T cells. Our study indicated that NK cells are critical to the control of the reservoir size, and TIGIT may be a target for enhancing the NK cell-mediated elimination of the reservoir.