Abstract
BackgroundCD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens. T cell receptors (TCR) reflect the composition and function of T cells. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF). The repertoire of TCR beta chain variable (TCRBV) regions of peripheral Tregs in ACLF patients is not well understood.MethodsHuman PBMCs were separated and sorted into CD4+CD25+ Treg subsets using density gradient centrifugation and magnetic activated cell sorting (MACS). The CD4+CD25high Treg frequency in peripheral blood of ACLF and chronic hepatitis B (CHB) patients was measured by flow cytometry. The molecular profiles of TCRBV CDR3 were determined using gene melting spectral pattern (GMSP) analysis. TCRBV gene families were cloned and sequenced when the GMSP profiles showed a single-peak.ResultsCD4+CD25high Treg prevalence in peripheral blood of ACLF patients is increased significantly compared to healthy donors (HDs) (P < 0.01) and CHB patients (P < 0.01). The prevalence of CD4+CD25high Tregs in ACLF or CHB patients is positively correlated with HBV DNA load. The TCRBV11, BV13.1, BV18, BV20 are the most prevalent TCRBV in CD4+CD25+ Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.ConclusionsThe CD4+CD25high Tregs prevalence in peripheral blood is indicative of disease severity in ACLF or CHB patients. The relatively conserved TCRBV20 CDR3 motif “TGTGHSPLH” and TCRBV11 CDR3 motif “VYNEQ” may be used in helping diagnosis and treat patients with ACLF.
Highlights
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens
We examined the frequency of peripheral CD4+CD25+ Tregs from HBVinfected acute-on-chronic liver failure (ACLF) patients, and the TCR beta chain variable (TCRBV) CDR3 repertoire in Tregs from ALCF and chronic hepatitis B (CHB) patients
Our results indicate that patients with Hepatitis B virus (HBV) related-ACLF had a significantly higher frequency of peripheral CD4+CD25high
Summary
CD4+CD25+ regulatory T cells (Tregs) play an important role in maintaining immunological tolerance to self and foreign antigens. It is not universally agreed that there is a relationship between CD4+CD25+ Treg frequency and the severity of acute-on-chronic liver failure (ACLF). Despite a reduction in new HBV infections since the introduction of vaccination in the early 1990s, there are approximately 350 million chronic HBV carriers worldwide, and HBV remains an important cause of liver disease in developed countries [1]. HBV infection can lead to a spectrum of liver diseases, including chronic asymptomatic HBV carrier (AsC), chronic hepatitis B (CHB), liver cirrhosis (LC) and hepatocellular carcinoma (HCC) or acute-on-chronic liver failure (ACLF) [2,3]. HBV-related ACLF is an acute decompensation of chronic liver disease due to precipitating events such as upper gastrointestinal (UGI) bleeding, ischemia, or additional superimposed liver injury due to alcohol, hepatotoxic drugs, surgical procedures, or reactivation of viral hepatitis [4]. The role of T-cell immunity in ACLF pathogenesis is receiving more attention, it is not well understood
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