{"doi":"10.1101/2025.07.02.25330735","title":"Functionality and phenotype of T cells in patients with varying severity of acute dengue and metabolic status","abstract":"Background: Currently the role of dengue virus (DENV) specific T cell responses in disease pathogenesis and protection are not well understood, including potential differences in those who have obesity. We sought to investigate the functionality and phenotype of T cells in patients with acute dengue fever (DF) or dengue haemorrhagic fever (DHF). Methods: T cell function was assessed in patients with DF (n=50) and DHF (n=12), recruited within ≤4 days of illness and again on day 5 to 7, using 109 peptides representing CD8+ epitopes and 90 peptides targeting CD4+ T cell epitopes. Phenotypic analysis was in DF (n=21) and DHF patients (n=21), recruited between days 6-8 since onset of illness, by multicolor flow cytometry. Results: The frequency of ex vivo IFNγ ELISpot responses to both the CD4+ and CD8+ peptides pools significantly increased from the first to second time point in patients with DF (p<0.0001) but not with DHF. The frequency of ex vivo IFNγ ELISpot responses to CD4+ (p=0.001) and CD8+ peptides pools (p=0.0002) also significantly increased from the first to second time point in lean patients compared obese patients. Cutaneous lymphocyte associated antigen (CLA) expression was significantly higher in the CD8+ T cell subset in patients with DF and DHF compared to HC and these differences were most significant in CD8+CD45RA- T cells. CD8+CD45RA-CLA+ T cells consisted of >50% of the T cells in 9/21 patients with DHF, with 92.7% expressing CD38. CLA expression was highest in the CD8+CD45RA- of obese individuals, which was significantly higher compared to lean individuals (p=0.01). CD27 and CD127 were both significantly downregulated in patients with DHF compared to DF, with ICOS expression being significantly higher in CD8+ T cells in DHF. Discussion: Patients with DHF and obese individuals had impaired T cell functionality. Activated and skin homing CD8+ T cells were associated with DHF, with downregulation of CD27 and CD127. Therefore, the role of skin homing T cells, which have impaired functionality in disease pathogenesis, should be further investigated.","journal":"medRxiv","year":2025,"id":569652,"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":0.9394,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1453505,"name":"Malithi De Silva","orcid":"0009-0001-3113-0954","position":1,"is_corresponding":false},{"id":1475154,"name":"Chathumini Dissanayake","orcid":null,"position":2,"is_corresponding":false},{"id":1475155,"name":"Radandee Rathnapriya","orcid":null,"position":3,"is_corresponding":false},{"id":495842,"name":"Ananda Wijewickrama","orcid":"0000-0003-2723-1813","position":4,"is_corresponding":false},{"id":1360134,"name":"Damayanthi Idampitiya","orcid":null,"position":5,"is_corresponding":false},{"id":778393,"name":"Chandima Jeewandara","orcid":"0000-0001-6830-5175","position":6,"is_corresponding":false},{"id":106119,"name":"Graham S. Ogg","orcid":"0000-0002-3097-045X","position":7,"is_corresponding":false},{"id":479263,"name":"Gathsaurie Neelika Malavige","orcid":"0000-0001-9201-0449","position":8,"is_corresponding":false},{"id":804530,"name":"Heshan Kuruppu","orcid":"0009-0005-8745-8202","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T02:57:03.510013Z","pmid":"40630582","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":[]}