TIM-3 as a marker of exhaustion in CD8+ T cells of active chronic hepatitis B patients

Microb Pathog. 2019 Mar:128:323-328. doi: 10.1016/j.micpath.2019.01.026. Epub 2019 Jan 17.

Abstract

Background: Chronic HBV infection presents weak or no virus-specific T-cell responses, implying to an exhausted phenotype, characterized by overexpression of several inhibitory receptors. In the present study, it was aimed to characterize the panel of inhibitory molecules on the CD8+ T cells in patients with active chronic HBV infection.

Methods: In this study, 31 active and 32 inactive individuals with chronic HBV infection were recruited. Peripheral blood mononuclear cells were isolated and a multicolor flow cytometry was applied to evaluate the surface inhibitory molecules of TIM3, PD-1, and CD39.

Results: CD8+ T cells expressing TIM3 were significantly higher in cases with active chronic HBV infection compared to inactive chronic HBV group (8.43 ± 1.4 vs. 5.15 ± 1.43; P < 0.0001). CD8+TIM3+PD-1+ T cells were significantly higher in active chronic HBV cases in comparison to the inactive chronic HBV subjects (4.26 ± 1.04 vs. 3.41 ± 0.74; P < 0.001). Different subpopulations of the CD8+ T cells were correlated with the duration of infection and HBV DNA load in the cases with active chronic HBV infection.

Conclusion: It appears that CD8+ TIM3+ T cells are the major exhausted phenotype of T cells during the active state of HBV infection.

Keywords: CD39; Flow cytometry; HBV; PD-1; TIM3.

MeSH terms

  • Adult
  • Apyrase / metabolism
  • Biomarkers*
  • CD8-Positive T-Lymphocytes / immunology*
  • CD8-Positive T-Lymphocytes / metabolism*
  • Female
  • Flow Cytometry
  • Hepatitis A Virus Cellular Receptor 2 / blood*
  • Hepatitis A Virus Cellular Receptor 2 / metabolism*
  • Hepatitis B virus / pathogenicity
  • Hepatitis B, Chronic / blood*
  • Hepatitis B, Chronic / immunology*
  • Humans
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism
  • Viral Load

Substances

  • Biomarkers
  • HAVCR2 protein, human
  • Hepatitis A Virus Cellular Receptor 2
  • PDCD1 protein, human
  • Programmed Cell Death 1 Receptor
  • Apyrase
  • ENTPD1 protein, human