Conclusion
Blocking TIGIT may be an effective strategy to invigorate antibody-dependent NK cell activity against HIV-1 activated in cellular reservoirs for cure or treatment strategies.
Methods
We measured TIGIT expression on immune cell subsets of 95 PLWH and assessed its impact on NK cell function, including elimination of autologous CD4+ T cells infected through reactivation of endogenous HIV-1.
Results
TIGIT was expressed on CD4+ T cells, CD8+ T cells and NK cells from PLWH. Although TIGIT levels on T cells correlated with HIV-1 disease progression, the extent of TIGIT expression on NK cells more closely paralleled adaptation to CMV. TIGIT interacts with its predominant ligand, poliovirus receptor (PVR), to inhibit effector cell functions. Circulating CD4+ T cells from PLWH more frequently expressed PVR than HIV-seronegative controls, and PVR expression was enriched in CD4+ T cells replicating HIV-1 ex vivo. Treatment with anti-TIGIT monoclonal antibodies increased NK cell HIV-1-specific antibody-dependent cytotoxicity in vitro and ex vivo.