title: T lymphocytes from chronic HCV-infected patients are primed for activation-induced apoptosis and express unique pro-apoptotic gene signature.
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.
authors.affiliation: Key Laboratory of Systems Biology of Pathogens, Ministry of Health, Institute of Pathogen Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, R. P. China.
authors.forename: Bin-Bin
authors.initials: BB
authors.lastname: Zhao
authors.forename: Su-Jun
authors.initials: SJ
authors.lastname: Zheng
authors.forename: Lu-Lu
authors.initials: LL
authors.lastname: Gong
authors.forename: Yu
authors.initials: Y
authors.lastname: Wang
authors.forename: Cai-Feng
authors.initials: CF
authors.lastname: Chen
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Jin
authors.forename: Ding
authors.initials: D
authors.lastname: Zhang
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Yuan
authors.forename: Jian
authors.initials: J
authors.lastname: Guo
authors.forename: Zhong-Ping
authors.initials: ZP
authors.lastname: Duan
authors.forename: You-Wen
authors.initials: YW
authors.lastname: He
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000276:immunology*; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*
chemical_list: D016207:Cytokines