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

Dong X, Gong Y, Zeng H, Hao Y, Wang X, Hou J, Wang J, Li J, Zhu Y, Liu H, Han J, Zhou H, Shen L, Gao T, Zhou T, Yang S, Li S, Chen Y, Meng Q, Li H.
Liver Int. 2013 Nov;33(10):1517-26. doi: 10.1111/liv.12248. Epub 2013 Jul 21.

Source

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.

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.

Conclusion

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.