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Chronic Hepatitis C Virus Infection Modulates the Transcriptional Profiles of CD4+ T Cells

Michal Holub1, Alžběta Stráníková1, Ondřej Beran1

  • 1Department of Infectious Diseases, First Faculty of Medicine, Charles University and Military University Hospital Prague, U Vojenské Nemocnice 1200, Praha 6 169 02, Czech Republic.

The Canadian Journal of Infectious Diseases & Medical Microbiology = Journal Canadien Des Maladies Infectieuses Et De La Microbiologie Medicale
|March 29, 2021
PubMed

Insights

Chronic hepatitis C (CHC) alters immune responses by decreasing Th2/Th17 cells and increasing regulatory T cells. This study characterizes these CD4+ T cell changes and myeloid-derived suppressor cells in CHC patients.

Area of Science:

  • Immunology
  • Hepatology
  • Virology

Background:

  • Chronic hepatitis C (CHC) is characterized by a dysregulated cell-mediated immune response.
  • Understanding T cell subset alterations is crucial for managing HCV infection.

Purpose of the Study:

  • To investigate functional changes in CD4+ T cell subsets and myeloid-derived suppressor cells (MDSCs) during chronic hepatitis C virus (HCV) infection.
  • To compare these immune parameters in CHC patients, individuals who cleared HCV, and healthy controls.

Main Methods:

  • Evaluated lineage-defining transcriptional factors (T-bet, Gata3, Rorγt, Foxp3) in CD4+ T cells and MDSC percentages in peripheral blood.
  • Utilized multicolor flow cytometry for intracellular and surface staining of peripheral blood mononuclear cells.
  • Included 33 CHC patients, 31 HCV-cleared individuals, and 30 healthy subjects.

Main Results:

  • CHC patients exhibited lower percentages of Gata3+ and Rorγt+ CD4+ T cells (Th2/Th17) and higher percentages of Foxp3+ CD4+ T cells (Tregs) compared to controls.
  • Elevated ratios of T-bet+/Gata3+ and Foxp3+/Rorγt+ CD4+ T cells were observed in CHC patients.
  • A negative correlation was found between activated CD8+ T cells (CD38+/HLA-DR+) and MDSC percentages in CHC patients.

Conclusions:

  • Chronic HCV infection leads to a shift in CD4+ T cell populations, characterized by reduced Th2/Th17 differentiation and increased Treg induction.
  • These immune dysregulations contribute to the suppressed immune response observed in chronic HCV infection.
  • Characterization of these T cell subsets and MDSCs offers insights into HCV pathogenesis and potential therapeutic targets.
Abstract

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