{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T03:19:33Z","timestamp":1783135173169,"version":"3.54.6"},"reference-count":58,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T00:00:00Z","timestamp":1725926400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH\/NINDS","award":["R01 NS097147"],"award-info":[{"award-number":["R01 NS097147"]}]},{"name":"NIH\/NINDS","award":["NeuroAIDS, NIH\/NIMH T32-MH079785"],"award-info":[{"award-number":["NeuroAIDS, NIH\/NIMH T32-MH079785"]}]},{"name":"Interdisciplinary and Translational Research Training","award":["R01 NS097147"],"award-info":[{"award-number":["R01 NS097147"]}]},{"name":"Interdisciplinary and Translational Research Training","award":["NeuroAIDS, NIH\/NIMH T32-MH079785"],"award-info":[{"award-number":["NeuroAIDS, NIH\/NIMH T32-MH079785"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/v16091443","type":"journal-article","created":{"date-parts":[[2024,9,10]],"date-time":"2024-09-10T09:10:57Z","timestamp":1725959457000},"page":"1443","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"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"],"prefix":"10.3390","volume":"16","author":[{"given":"Julie","family":"Joseph","sequence":"first","affiliation":[{"name":"Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2103-3421","authenticated-orcid":false,"given":"Thomas A.","family":"Premeaux","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Weill Cornel Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-1263-8222","authenticated-orcid":false,"given":"Ritesh","family":"Tandon","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Edward L.","family":"Murphy","sequence":"additional","affiliation":[{"name":"Departments of Laboratory Medicine and Epidemiology\/Biostatistics, University of California, San Francisco, CA 94143, USA"},{"name":"Vitalant Research Institute, San Francisco, CA 94105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta","family":"Bruhn","sequence":"additional","affiliation":[{"name":"Vitalant Research Institute, San Francisco, CA 94105, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-2869","authenticated-orcid":false,"given":"Christophe","family":"Nicot","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS 66103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2438-6716","authenticated-orcid":false,"given":"Bobby Brooke","family":"Herrera","sequence":"additional","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, Newark, NJ 07102, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases, and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Lemenze","sequence":"additional","affiliation":[{"name":"Molecular and Genomics Informatics Core, Rutgers New Jersey Medical School, Newark, NJ 07103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-0328-1277","authenticated-orcid":false,"given":"Reem","family":"Alatrash","sequence":"additional","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, Newark, NJ 07102, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases, and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8328-9062","authenticated-orcid":false,"given":"Prince","family":"Baffour Tonto","sequence":"additional","affiliation":[{"name":"Rutgers Global Health Institute, Rutgers University, Newark, NJ 07102, USA"},{"name":"Department of Medicine, Division of Allergy, Immunology, and Infectious Diseases, and Child Health Institute of New Jersey, Rutgers Robert Wood Johnson Medical School, Rutgers University, New Brunswick, NJ 08901, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5427-4187","authenticated-orcid":false,"given":"Lishomwa C.","family":"Ndhlovu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Infectious Diseases, Weill Cornel Medicine, New York, NY 10021, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9925-4259","authenticated-orcid":false,"given":"Pooja","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA"},{"name":"Department of Neurobiology and Anatomy, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,9,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1212\/CPJ.0000000000000832","article-title":"Management of HAM\/TSP: Systematic Review and Consensus-based Recommendations 2019","volume":"11","author":"Araujo","year":"2021","journal-title":"Neurol. 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