Both authors contributed equally to this paper.
Imbalance between circulating CD4+ regulatory T and conventional T lymphocytes in patients with HBV-related acute-on-chronic liver failure
Article first published online: 21 JUL 2013
© 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd
Volume 33, Issue 10, pages 1517–1526, November 2013
How to Cite
Liver Int. 2013; 33: 1517–1526
- Issue published online: 6 OCT 2013
- Article first published online: 21 JUL 2013
- Accepted manuscript online: 19 JUN 2013 12:40AM EST
- Manuscript Accepted: 11 JUN 2013
- Manuscript Revised: 11 APR 2013
- Manuscript Received: 1 OCT 2012
- National Nature Science Foundation of China. Grant Numbers: 30971333, 30770962, 81170421
- CD3+ T cells;
- CD4+ regulatory T lymphocytes;
- chronic hepatitis B;
- conventional T lymphocytes;
- HBV-related acute-on-chronic liver failure;
- septic shock
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.
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.
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.
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.