Synergistic upregulation of PD-1 and TIGIT is linked to increased inhibitory function (62, 63), poor functionality of HIV-1 specific T-cell responses (30) and is inversely correlated with CD4% and CD4/CD8 ration in HIV-1 infection (72), suggesting that this population resembles highly exhausted CD8 T-cells. The gene discussed is CD4; the disease is HIV-1 infection.