Decreased frequency of regulatory T cells related to liver injury in acute viral hepatitis (VIR5P.1032)

Abstract

Abstract FoxP3+ regulatory T cells (Tregs) are essential for maintaining self-tolerance and homeostasis in the immune system. Their role and character are already shown in many disease model, however, still concealed in acute viral hepatitis. In this study, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury. Using isolated peripheral blood mononuclear cells (PBMCs) of 62 AHA patients, the decreased frequency and attenuated function of Tregs were observed; those results were inversely correlated with the severity of liver damage, represented by serum alanine aminotransferase (ALT) level. In addition, the frequency and suppressive function of Tregs were recovered at the convalescence phase when serum ALT level was completely normalized. We found a cause of the reduced frequency of Tregs from elevated expression level of Fas receptor, related to apoptosis, on Tregs in AHA patients. Indeed, the Tregs of AHA patients were more susceptible to Fas-mediated apoptosis than those of healthy controls in vitro experiments. In present study, we demonstrate that the frequency and suppressive function of Tregs were attenuated during acute HAV infection, resulting from apoptosis of Tregs induced by Fas-mediated mechanism.