{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T10:36:04Z","timestamp":1776854164249,"version":"3.51.2"},"reference-count":30,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,21]],"date-time":"2026-04-21T00:00:00Z","timestamp":1776729600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) is a chronic inflammatory disease driven by HTLV-1-infected CD4+ T cells; however, the phenotypic and functional characteristics of disease-associated T-cell subsets remain incompletely understood. We analyzed samples using flow cytometry (n = 3\u20135 per group) and RNA-seq (n = 13), focusing on CADM1highCD4+ T cells enriched for HTLV-1-infected cells to evaluate a transferrin receptor (TfR)-expressing subset. TfR+CADM1highCD4+ T cells were detected in both asymptomatic carriers and patients with HAM, but their frequency among CD4+ T cells was higher in HAM patients. These cells exhibited a Treg-like phenotype with higher Foxp3 and CTLA-4 expression than TfR\u2212 cells and showed increased Ki-67 positivity, consistent with proliferation. Despite this phenotype, they produced interferon-\u03b3, indicating inflammatory potential, while Foxp3 expression was lower in HAM patients than in asymptomatic carriers, suggesting a more inflammatory phenotype. Furthermore, TfR transcript levels (RNA-seq TPM) correlated with clinical indicators of disease activity, including neopterin and CXCL10 protein levels, and the Osame motor disability score. Collectively, these findings suggest that TfR identifies a proliferative, Foxp3-low, Treg-like inflammatory CD4+ T-cell subset that is associated with disease activity in HAM.<\/jats:p>","DOI":"10.3390\/pathogens15040450","type":"journal-article","created":{"date-parts":[[2026,4,22]],"date-time":"2026-04-22T09:01:24Z","timestamp":1776848484000},"page":"450","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Transferrin Receptor Marks a Foxp3-Low Treg-like Inflammatory T Cell Subset Associated with Disease Severity in HAM\/TSP"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-1954-1248","authenticated-orcid":false,"given":"Shinsuke","family":"Nakajima","sequence":"first","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Masaki","family":"Hino","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norihiro","family":"Takenouchi","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7527-0345","authenticated-orcid":false,"given":"Yoshihisa","family":"Yamano","sequence":"additional","affiliation":[{"name":"Department of Rare Diseases Research, Institute of Medical Science, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Makoto","family":"Yamagishi","sequence":"additional","affiliation":[{"name":"Laboratory of Viral Oncology and Genomics, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 108-8639, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tokifumi","family":"Odaka","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"},{"name":"Central Research Center, Institute of Biomedical Science, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fhahira Rizkhika","family":"Admadiani","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecile","family":"Faye","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kaoru","family":"Uchimaru","sequence":"additional","affiliation":[{"name":"Laboratory of Tumor Cell Biology, Department of Computational Biology and Medical Sciences, Graduate School of Frontier Sciences, University of Tokyo, Tokyo 108-8639, Japan"},{"name":"Faculty of Medicine, Showa Medical University, Tokyo 142-8555, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun-Ichi","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-9719-0350","authenticated-orcid":false,"given":"Kazu","family":"Okuma","sequence":"additional","affiliation":[{"name":"Department of Microbiology, Faculty of Medicine, Kansai Medical University, Hirakata 573-1010, Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6476","DOI":"10.1073\/pnas.78.10.6476","article-title":"Adult T-Cell Leukemia: Antigen in an ATL Cell Line and Detection of Antibodies to the Antigen in Human Sera","volume":"78","author":"Hinuma","year":"1981","journal-title":"Proc. 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