{"doi":"10.3390/v16091443","title":"Dendritic Cells Pulsed with HAM/TSP Exosomes Sensitize CD4 T Cells to Enhance HTLV-1 Infection, Induce Helper T-Cell Polarization, and Decrease Cytotoxic T-Cell Response","abstract":"HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a progressive demyelinating disease of the spinal cord due to chronic inflammation. Hallmarks of disease pathology include dysfunctional anti-viral responses and the infiltration of HTLV-1-infected CD4+ T cells and HTLV-1-specific CD8+ T cells in the central nervous system. HAM/TSP individuals exhibit CD4+ and CD8+ T cells with elevated co-expression of multiple inhibitory immune checkpoint proteins (ICPs), but ICP blockade strategies can only partially restore CD8+ T-cell effector function. Exosomes, small extracellular vesicles, can enhance the spread of viral infections and blunt anti-viral responses. Here, we evaluated the impact of exosomes isolated from HTLV-1-infected cells and HAM/TSP patient sera on dendritic cell (DC) and T-cell phenotypes and function. We observed that exosomes derived from HTLV-infected cell lines (OSP2) elicit proinflammatory cytokine responses in DCs, promote helper CD4+ T-cell polarization, and suppress CD8+ T-cell effector function. Furthermore, exosomes from individuals with HAM/TSP stimulate CD4+ T-cell polarization, marked by increased Th1 and regulatory T-cell differentiation. We conclude that exosomes in the setting of HAM/TSP are detrimental to DC and T-cell function and may contribute to the progression of pathology with HTLV-1 infection.","journal":"Viruses","year":2024,"id":469107,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9488,"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":403005,"name":"Thomas A. Premeaux","orcid":"0000-0002-2103-3421","position":1,"is_corresponding":false},{"id":1302508,"name":"Ritesh Tandon","orcid":"0009-0006-1263-8222","position":2,"is_corresponding":false},{"id":447273,"name":"Edward L. Murphy","orcid":"0000-0001-6515-3989","position":3,"is_corresponding":false},{"id":324056,"name":"Roberta Bruhn","orcid":"0000-0002-5898-8168","position":4,"is_corresponding":false},{"id":484351,"name":"Christophe Nicot","orcid":"0000-0001-5927-2869","position":5,"is_corresponding":false},{"id":423703,"name":"Bobby Brooke Herrera","orcid":"0000-0002-2438-6716","position":6,"is_corresponding":false},{"id":300712,"name":"Alexander Lemenze","orcid":"0000-0003-3053-0849","position":7,"is_corresponding":false},{"id":1302509,"name":"Reem Alatrash","orcid":"0009-0002-0328-1277","position":8,"is_corresponding":false},{"id":1285197,"name":"Prince Baffour Tonto","orcid":"0000-0001-8328-9062","position":9,"is_corresponding":false},{"id":69472,"name":"Lishomwa C. Ndhlovu","orcid":"0000-0001-5427-4187","position":10,"is_corresponding":false},{"id":736093,"name":"Pooja Jain","orcid":"0000-0002-9925-4259","position":11,"is_corresponding":false},{"id":289800,"name":"Julie Joseph","orcid":"0000-0002-6920-0364","position":0,"is_corresponding":true}],"reference_count":62,"raw_metadata":null,"created_at":"2026-07-19T02:05:28.027781Z","pmid":"39339919","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":[]}