CD4 and chronic hepatitis C virus infection: Indeed, regulatory CD4+CD25+FoxP3+ T cells may contribute to T cell dysfunction in chronic hepatitis C and, indeed, blockade of Tim-3, another checkpoint molecule, on CD4+CD25+ T cells promoted the expansion of effector T cells more substantially than Tregs by improving STAT-5 signaling, thus correcting the imbalance of Foxp3+ Tregs/Foxp3− T effectors that was induced by HCV infection, in a manner similar to the PD-L1 blockade that upregulates STAT-5 phosphorylation in Tregs ex vivo [40].