T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature.

Published online

Journal Article

Although extensive studies have demonstrated the functional impairment of antigen-specific CD4(+) and CD8(+) T-cells during chronic hepatitis C virus (HCV) infection, the functional status of global CD4(+) and CD8(+) T-cells remains unclear. In this report, we recruited 42 long-term (~20 years) treatment-naïve chronic HCV (CHC) patients and 15 healthy donors (HDs) to investigate differences in global CD4(+) and CD8(+) T-cells function. We show that CD4(+) and CD8(+) T-cells from CHC patients underwent increased apoptosis after TCR stimulation. Furthermore, IFN-γ, IL-9 and IP-10 were elevated in CHC patients' plasma and promoted activation-induced T-cells death. Global CD4(+) and CD8(+) T-cells also showed unique transcriptional profiles in the expression of apoptosis-related genes. We identified BCL2, PMAIP1, and CASP1 in CD4(+) T-cells and IER3 and BCL2A1 in CD8(+) T-cells from CHC patients as HCV-specific gene signatures. Importantly, the gene expression patterns of CD4(+) and CD8(+) T-cells from CHC patients differ from those in CD4(+) and CD8(+) T-cells from human immunodeficiency virus type 1 (HIV-1) or hepatitis B virus (HBV) infected individuals. Our results indicate that chronic HCV infection causes a systemic change in cytokine levels that primes T-cells for activation-induced apoptosis. Furthermore, HCV infection programs unique apoptosis-related gene expression profiles in CD4(+) and CD8(+) T-cells, leading to their enhanced activation-induced apoptosis. These results provide novel insights to the pathogenesis of chronic HCV infection.

Full Text

Duke Authors

Cited Authors

  • Zhao, B-B; Zheng, S-J; Gong, L-L; Wang, Y; Chen, C-F; Jin, W-J; Zhang, D; Yuan, X-H; Guo, J; Duan, Z-P; He, Y-W

Published Date

  • 2013

Published In

Volume / Issue

  • 8 / 10

Start / End Page

  • e77008 -

PubMed ID

  • 24130824

Pubmed Central ID

  • 24130824

Electronic International Standard Serial Number (EISSN)

  • 1932-6203

Digital Object Identifier (DOI)

  • 10.1371/journal.pone.0077008

Language

  • eng

Conference Location

  • United States