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Dynamic changes of T cell receptor repertoires in patients with hepatitis B virus-related acute-on-chronic liver failure.

Abstract：

BACKGROUND AND AIMS:T cell-mediated immune injury plays a critical role in the pathogenesis of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF). Given the high short-term mortality and crucial role of T cells in the disease progression, it is necessary to investigate the dynamics of T cell clones during HBV-ACLF. The aim of this study was to longitudinally investigate dynamic changes in the composition and perturbation of T cell receptor β (TCRβ) chain repertoires and to determine whether TCR repertoire characteristics were associated with HBV-ACLF patient outcomes. METHODS:Peripheral blood mononuclear cells (PBMCs) were collected at two time points from 5 HBV-ACLF patients. Global CD4+ and CD8+ T cells were sorted using magnetic beads. TCRβ complementarity-determining region 3 was analyzed by unbiased high-throughput sequencing. RESULTS:During HBV-ACLF, there was a significant decrease in the diversity of T cell repertoires and an increase in proportion of the most 100 abundant clonotypes of CD8 T cells but not CD4. Decreased CD8 repertoire diversity was positively correlated with the reduction of the Model for End-Stage Liver Disease (MELD) score. CONCLUSIONS:There was significant clonal expansion in CD8 but not in CD4 T cell repertoires in HBV-ACLF patients during disease progression. Patients with greater clonal expansions in CD8 T cell repertoires may have better outcomes. CD8 TCRβ repertoire diversity may serve as a potential predictive marker for disease outcome.

journal_name

Hepatol Int

journal_title

Hepatology international

authors

Shen G,Sun S,Huang J,Deng H,Xu Y,Wang Z,Tang X,Gong X

doi

10.1007/s12072-019-10008-x

subject

Has Abstract

pub_date

2020-01-01 00:00:00

pages

47-56

issue

1

eissn

1936-0533

issn

1936-0541

pii

10.1007/s12072-019-10008-x

journal_volume

14

pub_type

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