Get access

Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in patients with HBV-related acute-on-chronic liver failure

Authors

  • Xiaojun Dong,

    1. 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
    Search for more papers by this author
    • Both authors contributed equally to this paper.
  • Yu Gong,

    1. 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
    Current affiliation:
    1. Department of Internal Medicine, Zhongshan Hospital, Fudan University, Shanghai, China
    Search for more papers by this author
    • Both authors contributed equally to this paper.
  • Hui Zeng,

    1. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Yu Hao,

    1. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Xianbo Wang,

    1. Beijing Ditan Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Jing Hou,

    1. ICU, Beijing Angen Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Jiefei Wang,

    1. ICU, Shanghai Public Health Clinical Center, Fudan University, Shanghai, China
    Search for more papers by this author
  • Juan Li,

    1. Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Yueke Zhu,

    1. Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Haixia Liu,

    1. Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Junyan Han,

    1. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Haiwei Zhou,

    1. Beijing Key Laboratory of Emerging Infectious Diseases, Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
  • Liwei Shen,

    1. 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
    Search for more papers by this author
  • Ting Gao,

    1. 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
    Search for more papers by this author
  • Tingting Zhou,

    1. 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
    Search for more papers by this author
  • Shuyin Yang,

    1. 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
    Search for more papers by this author
  • Shuting Li,

    1. 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
    Search for more papers by this author
  • Yingxuan Chen,

    1. 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
    Search for more papers by this author
  • Qinghua Meng,

    1. Department of Hepatology, Beijing You'an Hospital, Capital Medical University, Beijing, China
    Search for more papers by this author
    • Both authors contributed equally to this paper.
  • Hai Li

    Corresponding author
    • 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
    Search for more papers by this author
    • Both authors contributed equally to this paper.

Correspondence

Hai Li, Department of Gastroenterology, Renji Hospital, Shanghai Jiao-tong University School of Medicine, No. 1630 Dongfang Road, Shanghai 200127, China

Tel: +86 21 6320 0874

Fax: +86 21 6326 6027

e-mail: haili_17@126.com

Abstract

Background & Aims

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.

Ancillary