Phenotypes and clinical significance of circulating CD4 + CD25 + regulatory T cells (Tregs) in patients with acute-on-ch
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RESEARCH
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Phenotypes and clinical significance of circulating CD4+CD25+ regulatory T cells (Tregs) in patients with acute-on-chronic liver failure (ACLF) Jiezuan Yang1, Ping Yi1, Li Wei1, Zherong Xu2, Yunbo Chen1, Lingling Tang1 and Lanjuan Li1*
Abstract Background: CD4+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. Methods: Human 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. Results: CD4+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. Conclusions: The 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.
Background Hepatitis B virus (HBV) is responsible for chronic infection. 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]. * Correspondence: [email protected] 1 State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China Full list of author information is available at the end of the article
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 procedur
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