1. T Lymphocytes from Chronic HCV-Infected Patients Are Primed for Activation-Induced Apoptosis and Express Unique Pro-Apoptotic Gene Signature.
- Author
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Zhao, Bin-Bin, Zheng, Su-Jun, Gong, Lu-Lu, Wang, Yu, Chen, Cai-Feng, Jin, Wen-Jing, Zhang, Ding, Yuan, Xiao-Hui, Guo, Jian, Duan, Zhong-Ping, and He, You-Wen
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T cells , *HEPATITIS C virus , *HEPATITIS C , *APOPTOSIS , *CD4 antigen , *CD8 antigen , *GENE expression , *PATIENTS - Abstract
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. [ABSTRACT FROM AUTHOR]
- Published
- 2013
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