{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T09:47:51Z","timestamp":1782467271426,"version":"3.54.5"},"reference-count":50,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T00:00:00Z","timestamp":1780617600000},"content-version":"vor","delay-in-days":4,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Medical Virology"],"published-print":{"date-parts":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    HTLV\u20101\u2010associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) is a long\u2010term neuroinflammatory condition without effective therapy, partly due to limited understanding of its immunopathogenesis. Although higher HTLV\u20101 proviral load (PVL) is linked to disease susceptibility, the contribution of T\u2010cell immune checkpoints remains unclear. PD\u20101 and TIM\u20103 regulate T\u2010cell function, and evaluating them alongside cytokine balance may provide insight into disease mechanisms. This study included 30 HAM\/TSP patients, 30 HTLV\u20101 asymptomatic carriers, and 30 healthy controls. Distribution of PD\u20101 and TIM\u20103 across CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells was assessed by flow cytometry, serum IFN\u2010\u03b3 and IL\u201010 concentrations were quantified by ELISA, HTLV\u20101 proviral load quantification was performed using a SYBR Green\u2010based qPCR assay designed and validated in this study and viral subtypes were determined by LTR sequencing and drawing phylogenetic tree. Although CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells from HAM\/TSP cases displayed elevated PD\u20101 expression, TIM\u20103 expression was similar across groups. IFN\u2010\u03b3, but not IL\u201010, was elevated in HAM\/TSP. Increased PD\u20101\n                    <jats:sup>+<\/jats:sup>\n                    CD8\n                    <jats:sup>+<\/jats:sup>\n                    T\u2010cell frequency and IFN\u2010\u03b3 levels were associated with proviral load, motor disability, and disease duration. Elevated PD\u20101 expression without concurrent TIM\u20103 upregulation, together with high IFN\u2010\u03b3 levels, suggests a proinflammatory immune profile in HAM\/TSP rather than classical T\u2010cell exhaustion.\n                  <\/jats:p>","DOI":"10.1002\/jmv.71003","type":"journal-article","created":{"date-parts":[[2026,6,5]],"date-time":"2026-06-05T11:46:53Z","timestamp":1780660013000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PD\u20101 and TIM\u20103 Expression on Peripheral Blood T Cells in HTLV\u20101\u2010Associated Myelopathy\/Tropical Spastic Paraparesis (HAM\/TSP) and Their Correlations With Disease Stage and Proviral Load"],"prefix":"10.1002","volume":"98","author":[{"given":"Payam","family":"Siyadat","sequence":"first","affiliation":[{"name":"Biological Products and Blood Safety Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahtab","family":"Maghsudlu","sequence":"additional","affiliation":[{"name":"Biological Products and Blood Safety Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Kheirandish","sequence":"additional","affiliation":[{"name":"Biological Products and Blood Safety Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehdi","family":"Ajorloo","sequence":"additional","affiliation":[{"name":"Biological Products and Blood Safety Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fariba","family":"Zemorshidi","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Sheikhi","sequence":"additional","affiliation":[{"name":"Cancer Molecular Pathology Research Center Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zohreh","family":"Vahidi","sequence":"additional","affiliation":[{"name":"Immunology Research Center, Inflammation and Inflammatory Diseases Division Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reza","family":"Boostani","sequence":"additional","affiliation":[{"name":"Department of Neurology, Faculty of Medicine Mashhad University of Medical Sciences Mashhad Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6600-910X","authenticated-orcid":false,"given":"Zohreh","family":"Sharifi","sequence":"additional","affiliation":[{"name":"Biological Products and Blood Safety Research Center High Institute for Research and Education in Transfusion Medicine Tehran Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,5]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.micpath.2022.105622"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/tmi.13879"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2024.122973"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmicb.2012.00389"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/14737175.2023.2272639"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13365-020-00881-w"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-025-09635-2"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molimm.2021.06.001"},{"key":"e_1_2_10_10_1","first-page":"139","volume-title":"T cells in viral infections: The myriad flavours of antiviral immunity. 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