title: Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in patients with HBV-related acute-on-chronic liver failure.
abstract: OBJECTIVE
  The important pathophysiological role of immune dysfunction, especially innate immune dysfunction in patients with acute-on-chronic liver failure (ACLF), has been investigated in recent years, but dysregulation of adaptive immunity remains poorly elucidated. The aim of this study was to (i) determine the CD3(+) T-lymphocyte count and the balance between CD4(+) regulatory T (Tregs) and conventional T cells (Tconv) in hepatitis B virus (HBV)-related ACLF patients; (ii) analyse the frequencies of Tregs subpopulations; and (iii) assess the suppressive potency of CD4(+) Tregs and each fraction.
  
  
  METHODS
  We enrolled 20 HBV-ACLF patients, 10 septic shock subjects, 20 chronic hepatitis B (CHB) patients and 20 healthy volunteers (HC). Based on flow cytometry, we performed the absolute counting of circulating T lymphocytes and phenotyping of CD4(+) Tregs and quantified the effects of Tregs and each subpopulation on Tconv proliferation by CFSE staining.
  
  
  RESULTS
  Compared with CHB patients and HC, we observed an equal reduction in peripheral T subsets in HBV-ACLF and septic shock subjects; the number of CD4(+) Tregs remained unchanged and the Tconv count declined, promoting elevation of the Treg-to-Tconv ratio. The frequencies of Treg-II and -III were elevated in HBV-ACLF. Functional studies showed that the suppressive capacity of Tregs was preserved in the HBV-ACLF group and Treg-II came first.
  
  
  CONCLUSIONS
  Similar to septic shock subjects, in HBV-ACLF patients there exists a reduction in CD4(+) T lymphocytes, predominantly CD4(+) Tconv, and the development of suppressive CD4(+) Tregs greatly prevails over Tconv, constituting important characteristics of adaptive immune dysfunction of HBV-ACLF.
authors.affiliation: Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai Institute of Digestive Disease, Key Laboratory of Gastroenterology & Hepatology in Ministry of Health, Shanghai, China.
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Dong
authors.forename: Yu
authors.initials: Y
authors.lastname: Gong
authors.forename: Hui
authors.initials: H
authors.lastname: Zeng
authors.forename: Yu
authors.initials: Y
authors.lastname: Hao
authors.forename: Xianbo
authors.initials: X
authors.lastname: Wang
authors.forename: Jing
authors.initials: J
authors.lastname: Hou
authors.forename: Jiefei
authors.initials: J
authors.lastname: Wang
authors.forename: Juan
authors.initials: J
authors.lastname: Li
authors.forename: Yueke
authors.initials: Y
authors.lastname: Zhu
authors.forename: Haixia
authors.initials: H
authors.lastname: Liu
authors.forename: Junyan
authors.initials: J
authors.lastname: Han
authors.forename: Haiwei
authors.initials: H
authors.lastname: Zhou
authors.forename: Liwei
authors.initials: L
authors.lastname: Shen
authors.forename: Ting
authors.initials: T
authors.lastname: Gao
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhou
authors.forename: Shuyin
authors.initials: S
authors.lastname: Yang
authors.forename: Shuting
authors.initials: S
authors.lastname: Li
authors.forename: Yingxuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Qinghua
authors.initials: Q
authors.lastname: Meng
authors.forename: Hai
authors.initials: H
authors.lastname: Li
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D002681:China; D058625:End Stage Liver Disease / Q000209:etiology* / Q000276:immunology*; D005260:Female; D005434:Flow Cytometry; D005452:Fluoresceins; D019694:Hepatitis B, Chronic / Q000150:complications*; D006801:Humans; D016130:Immunophenotyping; D017114:Liver Failure, Acute / Q000209:etiology* / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D012772:Shock, Septic / Q000276:immunology; D013388:Succinimides; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*
chemical_list: C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D013388:Succinimides
keywords: CD3+ T cells; CD4+ regulatory T lymphocytes; HBV-related acute-on-chronic liver failure; chronic hepatitis B; conventional T lymphocytes; septic shock