TY - JOUR T1 - Liver injury in acute hepatitis A is associated with decreased frequency of regulatory T cells caused by Fas-mediated apoptosis JF - Gut JO - Gut SP - 1303 LP - 1313 DO - 10.1136/gutjnl-2013-306213 VL - 64 IS - 8 AU - Yoon Seok Choi AU - Jeewon Lee AU - Hyun Woong Lee AU - Dong-Yeop Chang AU - Pil Soo Sung AU - Min Kyung Jung AU - Jun Yong Park AU - Ja Kyung Kim AU - Jung Il Lee AU - Hana Park AU - Jae Youn Cheong AU - Kyung-Suk Suh AU - Hyung Joon Kim AU - June Sung Lee AU - Kyung-Ah Kim AU - Eui-Cheol Shin Y1 - 2015/08/01 UR - http://gut.bmj.com/content/64/8/1303.abstract N2 - Objective Foxp3+CD4+CD25+ regulatory T cells (Tregs) control immune responses, but their role in acute viral hepatitis remains elusive. Herein, we investigated alteration in the peripheral blood Treg population during acute hepatitis A (AHA) and its implication in the immune-mediated liver injury.Design The study included 71 patients with AHA, and peripheral blood mononuclear cells (PBMCs) were isolated. The suppressive activity of Treg population was determined by assessing anti-CD3/CD28-stimulated proliferation of Treg-depleted and reconstituted PBMCs. Treg cell frequency, phenotype and apoptosis in PBMCs were analysed by flow cytometry.Results The frequency of circulating Tregs was reduced during AHA. Moreover, the suppressive activity of the total Treg pool in the peripheral blood was attenuated during AHA. Treg frequency and suppressive activity of the Treg population inversely correlated with the serum alanine aminotransferase level. Fas was overexpressed on Tregs during AHA, suggesting their susceptibility to Fas-induced apoptosis. Indeed, increased apoptotic death was observed in Tregs of patients with AHA compared with healthy controls. In addition, agonistic anti-Fas treatment further increased apoptotic death of Tregs from patients with AHA. The decreased Treg frequency and Fas overexpression on Tregs were not observed in other acute liver diseases such as acute hepatitis B, acute hepatitis C and toxic/drug-induced hepatitis.Conclusions The size of the Treg pool was contracted during AHA, resulting from apoptosis of Tregs induced by a Fas-mediated mechanism. Decrease in Treg numbers led to reduced suppressive activity of the Treg pool and consequently resulted in severe liver injury during AHA. ER -