Myeloid cell-like transcript 2 is related to liver inflammation and the pathogenesis of hepatitis B via the involvement of CD8+T cell activation

Clin Exp Med. 2019 Feb;19(1):93-104. doi: 10.1007/s10238-018-0534-1. Epub 2018 Oct 25.

Abstract

This study analysed the biological significance of TLT-2 on CD8+T cells in hepatitis B patients and provided a theoretical basis for the potential role of TLT-2 as an immune regulator. Flow cytometry sorting, isobaric tags for relative and absolute quantitation and short hairpin RNAs were used to analyse the function of TLT-2 on CD8+T cells in hepatitis B patients. The TLT-2 expression levels in the acute hepatitis B and chronic hepatitis B groups were significantly higher than that in the healthy control group and were positively correlated with ALT and AST. The CD8+TLT-2+T cells exhibited stronger immune function and greater cell proliferation ability and secreted higher levels of cytokines than the CD8+TLT-2-T cells. An analysis of the proteome differences between the TLT-2+CD8+T and TLT-2-CD8+T cells revealed that TLT-2 affected CD8+T cell activation by regulating Granzyme B expression and by further action on the NF-κB signalling pathway. This study first elucidated the mechanism by which TLT-2 influences the activation of CD8+T cells, improved the understanding of the TLT-2 signalling pathway and clarified the role of the TLT-2+CD8+T cell subset in hepatitis B virus infection. The study proposed a novel subset of CD8+T cells that could be useful for understanding the immune function of patients with hepatitis B and further elucidating the pathogenesis of hepatitis B by analysing changes in this subpopulation with the goal of providing a new target for the treatment of hepatitis B.

Keywords: CD8+T; Cell activation; Costimulation; Inflammation; TLT-2.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Aspartate Aminotransferases / blood
  • CD8-Positive T-Lymphocytes / chemistry
  • CD8-Positive T-Lymphocytes / immunology*
  • Cell Proliferation
  • Cytokines / metabolism
  • Female
  • Flow Cytometry
  • Hepatitis B / pathology*
  • Humans
  • Lymphocyte Activation*
  • Male
  • Middle Aged
  • Proteome / analysis
  • Receptors, Immunologic / analysis*

Substances

  • Cytokines
  • Proteome
  • Receptors, Immunologic
  • TREML2 protein, human
  • Aspartate Aminotransferases
  • Alanine Transaminase