CD4 and immune system disorder: Similar to inhibitory molecules, PD-1 and CTLA-4 can regulate the expansion and restoration of HCV-specific CD4+ T cells in patients with chronic HCV infection,86and the loss of proliferative function followed by deletion of HCV-specific CD4+ T cells is closely related to HCV viremia.87 Upregulation of inhibitory molecules including PD-1 and CTLA-4 were also observed on HIV-specific CD4+ T cells correlating with disease progression and defining a reversible immune dysfunction,58, 88 which will help to interpret the related phenotype and mechanism found in HBV-infected patients.