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

Background: Chronic hepatitis C (CHC) is associated with altered cell-mediated immune response.
Objective: The aim of the study was to characterize functional alterations in CD4 ⁺ T cell subsets and myeloid-derived suppressor cells (MDSCs) during chronic hepatitis C virus (HCV) infection. Methodology . The expression levels of the lineage-defining transcriptional factors (TFs) T-bet, Gata3, Ror γ t, and Foxp3 in circulating CD4 ⁺ T cells and percentages of MDSCs in peripheral blood were evaluated in 33 patients with CHC, 31 persons, who had spontaneously cleared the HCV infection, and 30 healthy subjects. Analysis . The CD4+ T cells TFs T-bet (T-box expressed in T cells), Foxp3 (Forkhead box P3 transcription factor), Gata3 (Gata-binding protein 3), and Ror γ t (retinoic-acid-related orphan receptor gamma) and activation of CD8+ T cells, as well as percentages of MDSCs, were measured by multicolor flow cytometry after intracellular and surface staining of peripheral blood mononuclear cells with fluorescent monoclonal antibodies.
Result: The patients with CHC had significantly lower percentages of CD4 ⁺ T cells expressing Ror γ t and Gata3 and higher percentages of Foxp3-expressing CD4 ⁺ T cells than healthy controls and persons who spontaneously cleared HCV infection. The ratios of T-bet ⁺ /Gata3 ⁺ and Foxp3 ⁺ /Ror γ t ⁺ CD4 ⁺ T cells were the highest in the patients with CHC. In the patients with CHC, the percentages of Gata3 ⁺ and Ror γ t ⁺ CD4 ⁺ T cells and the percentages of T-bet ⁺ CD4 ⁺ T cells and CD38 ⁺ /HLA-DR ⁺ CD8 ⁺ T cells demonstrated significant positive correlations. In addition, the percentage of CD38 ⁺ /HLA-DR ⁺ CD8 ⁺ T cells correlated negatively with the percentage of MDSCs.
Conclusion: Chronic HCV infection is associated with downregulation of TFs Gata3 and Ror γ t polarizing CD4+ T cells into Th2 and Th17 phenotypes together with upregulation of Foxp3 responsible for induction of regulatory T cells suppressing immune response.
Competing Interests: The authors declare that there are no conflicts of interest.
(Copyright © 2021 Michal Holub et al.)