{"doi":"10.31083/j.fbl2903128","title":"Chronic Viral Infection Compromises the Quality of Circulating Mucosal–Associated Invariant T Cells and Follicular T Helper Cells via Expression of Inhibitory Receptors","abstract":"BACKGROUND: Chronic viral infection results in impaired immune responses rendering viral persistence. Here, we compared the quality of T-cell responses among chronic hepatitis B virus (HBV), hepatitis C virus (HCV) and human immunodeficiency virus (HIV)-infected individuals by examining the levels of expression of selected immune activation and exhaustion molecules on circulating MAIT cells and Tfh cells. METHODS: Cytokines were measured using a commercial Bio-plex Pro Human Cytokine Grp I Panel 17-plex kit (BioRad, Hercules, CA, USA). Inflammation was assessed by measuring an array of plasma cytokines, and phenotypic alterations in CD4+ T cells including circulating Tfh cells, CD8+ T cells, and TCR iVα7.2+ MAIT cells in chronic HBV, HCV, and HIV-infected patients and healthy controls. The cells were characterized based on markers pertaining to immune activation (CD69, ICOS, and CD27) proliferation (Ki67), cytokine production (TNF-α, IFN-γ) and exhaustion (PD-1). The cytokine levels and T cell phenotypes together with cell markers were correlated with surrogate markers of disease progression. RESULTS: The activation marker CD69 was significantly increased in CD4+hi T cells, while CD8+ MAIT cells producing IFN-γ were significantly increased in chronic HBV, HCV and HIV infections. Six cell phenotypes, viz., TNF-α+CD4+lo T cells, CD69+CD8+ T cells, CD69+CD4+ MAIT cells, PD-1+CD4+hi T cells, PD-1+CD8+ T cells, and Ki67+CD4+ MAIT cells, were independently associated with decelerating the plasma viral load (PVL). TNF-α levels showed a positive correlation with increase in cytokine levels and decrease in PVL. CONCLUSION: Chronic viral infection negatively impacts the quality of peripheral MAIT cells and Tfh cells via differential expression of both activating and inhibitory receptors.","journal":"Frontiers in Bioscience-Landmark","year":2024,"id":475093,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9536,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":435766,"name":"Yean K. Yong","orcid":"0000-0002-8409-6251","position":1,"is_corresponding":false},{"id":364797,"name":"Amudhan Murugesan","orcid":"0000-0003-4713-2927","position":2,"is_corresponding":false},{"id":537129,"name":"Hong Yien Tan","orcid":null,"position":3,"is_corresponding":false},{"id":1185585,"name":"Ying Zhang","orcid":"0000-0002-8982-8407","position":4,"is_corresponding":false},{"id":1311950,"name":"Ashwin Rajeev","orcid":"0009-0005-4383-2573","position":5,"is_corresponding":false},{"id":961492,"name":"Sivadoss Raju","orcid":"0000-0002-0524-2979","position":6,"is_corresponding":false},{"id":432913,"name":"Pachamuthu Balakrishnan","orcid":"0000-0002-1710-9155","position":7,"is_corresponding":false},{"id":435768,"name":"Marie Larsson","orcid":"0000-0002-4524-0177","position":8,"is_corresponding":false},{"id":280890,"name":"Vijayakumar Velu","orcid":"0000-0003-4238-1924","position":9,"is_corresponding":false},{"id":340123,"name":"Esaki M. Shankar","orcid":"0000-0002-7866-9818","position":10,"is_corresponding":false},{"id":961490,"name":"Jaisheela Vimali","orcid":"0009-0002-1607-1658","position":0,"is_corresponding":true}],"reference_count":30,"raw_metadata":null,"created_at":"2026-07-19T02:06:16.992586Z","pmid":"38538288","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":[]}