Phenotypes and clinical significance of circulating CD4 CD25 regulatory T cells Tregs in patients with acute-on-chronic liver failure ACLFReport as inadecuate

Phenotypes and clinical significance of circulating CD4 CD25 regulatory T cells Tregs in patients with acute-on-chronic liver failure ACLF - Download this document for free, or read online. Document in PDF available to download.

Journal of Translational Medicine

, 10:193



BackgroundCD4CD25 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 CD4CD25 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 CD4CD25 Treg subsets using density gradient centrifugation and magnetic activated cell sorting MACS. The CD4CD25 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.

ResultsCD4CD25 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 CD4CD25 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 CD4CD25 Tregs in ACLF and CHB patients. In addition, the CDR3 motifs were relatively conserved in these four TCRBV gene families.

ConclusionsThe CD4CD25 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.

AbbreviationsACLFAcute-on-chronic liver failure

ALTAlanine amino transferase

ASTAspartate amino transferase

CHBChronic hepatitis B

FoxP3Anti-forkhead family transcription factor 3

HBVHepatitis B virus

HBsAgHepatitis B surface antigen

HBeAgHepatitis B envelope antigen

Real-time-PCRReal-time fluorescent quantitative polymerase chain reaction

GMSPGene melting spectral pattern

TBiLTotal bilirubin.

Electronic supplementary materialThe online version of this article doi:10.1186-1479-5876-10-193 contains supplementary material, which is available to authorized users.

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Author: Jiezuan Yang - Ping Yi - Li Wei - Zherong Xu - Yunbo Chen - Lingling Tang - Lanjuan Li


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