RT Journal Article SR Electronic 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 FD BMJ Publishing Group Ltd and British Society of Gastroenterology SP 1303 OP 1313 DO 10.1136/gutjnl-2013-306213 VO 64 IS 8 A1 Yoon Seok Choi A1 Jeewon Lee A1 Hyun Woong Lee A1 Dong-Yeop Chang A1 Pil Soo Sung A1 Min Kyung Jung A1 Jun Yong Park A1 Ja Kyung Kim A1 Jung Il Lee A1 Hana Park A1 Jae Youn Cheong A1 Kyung-Suk Suh A1 Hyung Joon Kim A1 June Sung Lee A1 Kyung-Ah Kim A1 Eui-Cheol Shin YR 2015 UL http://gut.bmj.com/content/64/8/1303.abstract AB 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.