Liver injury is associated with enhanced regulatory T‐cell activity in patients with chronic hepatitis B

Abstract

Chronic hepatitis B virus (HBV) infection is associated with impairment of HBV-specific immune responses. Recently, it has been shown that regulatory T (Treg) cells downregulate HBV-specific immune responses but their role in chronic hepatitis B is still controversial. We hypothesized that liver injury enhances the influence of Treg cells on HBV-specific immune responses. The frequency of Treg cell and the in vitro expansion of HBV-specific CD8+ T cell detected by the tetramer method were investigated in 79 patients with chronic hepatitis B. Thirty-three healthy volunteers were enrolled to measure the frequency of Treg cell as controls. The results showed that in chronic hepatitis B cases, the frequency of Treg cells in peripheral blood was significantly higher than that in normal volunteers. The higher level of serum transaminase was associated with higher frequency of Treg cells, which both had a linear correlation relationship. HBV-DNA level, HBe status, age and sex had no statistical association with Treg cell frequency. Furthermore, in patients with higher serum transaminase levels, the expansion of HBV-specific CD8+ T cells was higher after removal of Treg cells when compared with patients with lower serum transaminase levels. In conclusion, our data indicate a significant association between serum transaminase level and frequency/activity of Treg cells. Based on this observation, we propose that liver-injury enhances Treg cell frequency/activity in chronic hepatitis B patients.

LncRNA HULC affects the differentiation of Treg in HBV-related liver cirrhosis

“…To address these issues, a sustained effort to uncover the cellular and molecular basis of HBV-related liver cirrhosis is paid [14]. Recently, studies have shown that Th1 cells [15], Th17 cells [16], Tregs [17], Kupffer cells [15], monocytes, natural killer cells [18], and other immune cells are involved in pathological HBV-related liver cirrhosis. Increase of Tregs and other cells in the PBMC lead to higher levels of transforming growth factor-β (TGF-β).…”

Regulatory T cells differentially modulate the maturation and apoptosis of human CD8+ T-cell subsets

“…In these situations, it is not clear whether Treg cells are "friends" or "foes," leading to a suppression of tissue damage mediated by virusspecific effector cells or inhibition of host immunity. 43 The accumulation of Treg cells in the settings of uncontrolled infection, as well as their ability to strongly inhibit the antigen-specific proliferation and effector functions, have been demonstrated in several human and animal model infections: HIV, 15,16,19,20 hepatitis B virus (HBV), 15,16,19,20,44,45 hepatitis C virus (HCV), 17,45,46 tuberculosis, 47 and simian immunodeficiency virus (SIV). 48 Lack of control of viral replication by specific CD8 ϩ T cells has been explained by a skewed differentiation program resulting either in accumulation of immature and poorly functional effectors as shown in HIV ϩ subjects, [49][50][51] or in excessive differentiation and exhaustion of the effector potential, typical of active CMV.…”

Human CD4 and CD8 regulatory T cells in infectious diseases and vaccination

“…Increased numbers of circulating CD4 ϩ CD25 HI cells at the time of infection have been described in hepatitis B [59,60] and human papillomavirus (HPV) [61][62][63] infections. In lymph nodes and tumors from patients with HPV-induced malignancies, CD4 ϩ CD25 ϩ Tregs are present that are specific for HPV antigens [63].…”