{"doi":"10.17615/ejmw-kz14","title":"Hepatitis C virus core protein triggers expansion and activation of CD4+CD25+ regulatory T cells in chronic hepatitis C patients","abstract":"CD4+CD25+FoxP3+ regulatory T cells (Tregs) are increased in patients with chronic hepatitis C, which may contribute to the sustained suppression of hepatitis C virus (HCV)-specific T-cell responses and viral persistence in HCV-infected individuals. We postulated that HCV core protein (HCVc) directly contributes to the expansion of Tregs in HCV-infected patients, and we provide evidence to support this hypothesis in the report. Peripheral blood mononuclear cells (PBMCs) and sera were collected from 87 treatment-naïve chronic HCV-infected patients, CD4+CD25+ Tregs were measured by flow cytometry, and HCV RNA and HCVc levels were detected using qPCR and enzyme-linked immunosorbent assay (ELISA), respectively. CD4+, CD8+, CD4+CD25+ and CD4+CD25− T cells were purified from healthy donors and cultured with recombinant HCVc and Toll-like receptor (TLR) ligands. Flow cytometry was used to analyze cell proliferation, and ELISA was performed to measure cytokine production. In the 87 chronic HCV-infected patients, HCVc showed a significant correlation with HCV RNA and CD4+CD25+ Tregs. Mechanistic studies showed that HCVc, together with anti-CD3 antibody, augmented CD4+CD25+ Treg proliferation, but inhibited CD4+CD25− T-cell proliferation and IFN-γ production, in a dose-dependent and Treg-dependent manner. Moreover, unlike the TLR3 ligand (poly I:C) and the TLR4 ligand (lipopolysaccharide, LPS), the TLR2 ligand (lipoteichoic acid, LTA) and HCVc both inhibited TCR-induced CD4+ T-cell proliferation and IFN-γ secretion in a Treg-dependent manner. These data indicate that HCVc, like other TLR2 ligands, triggers CD4+CD25+ Treg activation and expansion to inhibit host immune responses, which may play a critical role in viral persistence in HCV-infected patients.","journal":"UNC Libraries","year":2020,"id":135700,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9491,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":544073,"name":"Ian Nicholas Crispe","orcid":"0000-0003-2375-5863","position":1,"is_corresponding":false},{"id":544070,"name":"Zhengkun Tu","orcid":"0000-0001-6803-2015","position":2,"is_corresponding":false},{"id":544068,"name":"Tianyang Li","orcid":"0000-0003-1662-3221","position":3,"is_corresponding":false},{"id":593249,"name":"Haijun Li","orcid":"0009-0002-9143-6653","position":4,"is_corresponding":false},{"id":545025,"name":"Hongxiao Song","orcid":null,"position":5,"is_corresponding":false},{"id":545023,"name":"Naicui Zhai","orcid":null,"position":6,"is_corresponding":false},{"id":544069,"name":"Junqi Niu","orcid":"0000-0001-5415-2024","position":7,"is_corresponding":false},{"id":593849,"name":"Xia Jin","orcid":null,"position":8,"is_corresponding":false},{"id":593250,"name":"Xiumei Chi","orcid":"0000-0002-6291-8496","position":9,"is_corresponding":false},{"id":255662,"name":"Lishan Su","orcid":"0000-0002-0350-5560","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T23:16:35.237665Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}