We have previously identified and characterised negative regulation of adaptive immune responses mediated by CTLA-4-expressing CD4+ T cells in the settings of acute liver failure (ALF).34 Taken together, our studies suggest a major immunomodulatory role of CTLA-4 in ALF and chronic liver failure and that blockade of this pathway may be beneficial in restoring T cell-mediated responses. The gene discussed is CD4; the disease is chronic liver failure.