{"doi":"10.17615/ypb2-rw92","title":"Dengue virus infection elicits highly polarized CX3CR1+ cytotoxic CD4+ T cells associated with protective immunity","abstract":"Dengue virus (DENV) is a rapidly spreading pathogen with unusual pathogenesis, and correlates of protection from severe dengue disease and vaccine efficacy have not yet been established. Although DENV-specific CD8+ T-cell responses have been extensively studied, the breadth and specificity of CD4+ T-cell responses remains to be defined. Here we define HLA-restricted CD4+ T-cell epitopes resulting from natural infection with dengue virus in a hyperepidemic setting. Ex vivo flow-cytometric analysis of DENV-specific CD4+ T cells revealed that the virus-specific cells were highly polarized, with a strong bias toward a CX3CR1+ Eomesodermin+ perforin+ granzyme B+ CD45RA+ CD4 CTL phenotype. Importantly, these cells correlated with a protective HLA DR allele, and we demonstrate that these cells have direct ex vivo DENV-specific cytolytic activity. We speculate that cytotoxic dengue-specific CD4+ T cells may play a role in the control of dengue infection in vivo, and this immune correlate may be a key target for dengue virus vaccine development.","journal":"UNC Libraries","year":2020,"id":76602,"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":21,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9511,"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":393808,"name":"A. Sette","orcid":null,"position":1,"is_corresponding":false},{"id":399572,"name":"De Silva","orcid":"0000-0001-7535-141X","position":2,"is_corresponding":false},{"id":400890,"name":"D.J. Bangs","orcid":null,"position":3,"is_corresponding":false},{"id":393804,"name":"D. Weiskopf","orcid":null,"position":4,"is_corresponding":false},{"id":400891,"name":"B. H. Peters","orcid":null,"position":5,"is_corresponding":false},{"id":400892,"name":"R.V. Kolla","orcid":null,"position":6,"is_corresponding":false},{"id":400893,"name":"S. Crotty","orcid":null,"position":7,"is_corresponding":false},{"id":393818,"name":"J. Sidney","orcid":null,"position":8,"is_corresponding":false},{"id":400889,"name":"A.D. De Silva","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-18T21:48:27.511277Z","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":[]}