Yoon Seok Choi1, Jeewon Lee2, Hyun Woong Lee3, Dong-Yeop Chang2, Pil Soo Sung2, Min Kyung Jung2, Jun Yong Park4, Ja Kyung Kim4, Jung Il Lee4, Hana Park5, Jae Youn Cheong6, Kyung-Suk Suh7, Hyung Joon Kim3, June Sung Lee8, Kyung-Ah Kim8, Eui-Cheol Shin2. 1. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea Department of Internal Medicine, Chungnam National University College of Medicine, Daejeon, Republic of Korea. 2. Laboratory of Immunology and Infectious Diseases, Graduate School of Medical Science and Engineering, KAIST, Daejeon, Republic of Korea. 3. Department of Internal Medicine, Chung-Ang University College of Medicine, Seoul, Republic of Korea. 4. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Republic of Korea. 5. Department of Internal Medicine, CHA Bundang Medical Center, CHA University, Seongnam, Republic of Korea. 6. Department of Gastroenterology, Ajou University School of Medicine, Suwon, Republic of Korea. 7. Department of Surgery, Seoul National University College of Medicine, Seoul, Republic of Korea. 8. Department of Internal Medicine, Ilsan Paik Hospital, Inje University College of Medicine, Goyang, Republic of Korea.
Abstract
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
Authors: I Che Feng; Szu Jen Wang; Ming Jen Sheu; Lok-Beng Koay; Ching Yih Lin; Chung Han Ho; Chi Shu Sun; Hsing Tao Kuo Journal: World J Gastroenterol Date: 2015-11-28 Impact factor: 5.742
Authors: Katsuyoshi Shimozawa; Laura Contreras-Ruiz; Sofia Sousa; Ruan Zhang; Urvashi Bhatia; Kerry C Crisalli; Lisa L Brennan; Laurence A Turka; James F Markmann; Eva C Guinan Journal: Am J Transplant Date: 2021-09-27 Impact factor: 9.369