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

Author:

Holub Michal1ORCID,Stráníková Alžběta1,Beran Ondřej1,Arientová Simona1,Bartoš Oldřich12,Kondelková Kateřina3,Plíšek Stanislav4,Chalupa Pavel5

Affiliation:

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

2. Institute of Animal Physiology and Genetics, Laboratory of Fish Genetics, Czech Academy of Sciences, Liběchov, Czech Republic

3. Institute of Clinical Immunology, Faculty of Medicine in Hradec Králové, Charles University, Sokolská 581, Hradec Králové 500 05, Czech Republic

4. Department of Infectious Diseases, Faculty of Medicine, Charles University and University Hospital, Sokolská 581, Hradec Králové 500 05, Czech Republic

5. Department of Infectious and Tropical Diseases, First Faculty of Medicine, Charles University and University Hospital Bulovka, Budínova 2, Praha 8 180 81, Czech Republic

Abstract

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, Rorγt, 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 Rorγt (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 Rorγt 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+/Rorγt+ CD4+ T cells were the highest in the patients with CHC. In the patients with CHC, the percentages of Gata3+ and Rorγt+ 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 Rorγt polarizing CD4+ T cells into Th2 and Th17 phenotypes together with upregulation of Foxp3 responsible for induction of regulatory T cells suppressing immune response.

Funder

Ministerstvo Zdravotnictví Ceské Republiky

Publisher

Hindawi Limited

Subject

Infectious Diseases,Microbiology (medical)

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