{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T09:25:22Z","timestamp":1787131522540,"version":"build-2736575974"},"reference-count":56,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100005639","name":"Universidade De S\u00e3o Paulo","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100005639","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Immunol Res"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    HTLV-1 infection causes chronic immune activation and a prolonged asymptomatic phase, but the functional features that define early disease remain unclear. We evaluated whether spontaneous proliferation (SP) and related functional immune parameters can distinguish clinical stages across the HTLV-1 spectrum. Spontaneous and mitogen-induced lymphoproliferation (PHA, anti-CD3), measured by CFSE dilution, and in vitro cell death, measured by cytometry, were assessed in 435 HTLV-1-infected individuals: asymptomatic carriers (AC,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009303), individuals with intermediate syndrome (IS,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200921), patients with HTLV-1-associated myelopathy (HAM,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200994), adult T-cell leukemia\/lymphoma (ATL,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u200917), and two control groups. Notably, SP levels divided the asymptomatic individuals in two subgroups: low-SP (24.5%), similar to the control groups, and high-SP (75.5%), resembling IS, HAM, and ATL patients. Additionally, high-SP AC and HTLV-1 symptomatic groups showed significantly reduced responses to PHA and increased spontaneous and PHA-stimulated cell death, all features also observed in IS, HAM, and ATL patients, while low-SP AC results mirrored those of control groups. This increased cell death is strongly correlated with upregulation of Fas and FasL, especially in lymphocytes from high-SP AC, which may underlie the chronic activation and susceptibility to cell death. These findings suggest that HTLV-1 AC comprises two distinct subgroups: one with high SP and cell death, likely due to ongoing viral activity and immune alterations, and another with low SP, low viral activity, and preserved immune homeostasis. Follow up studies of AC with these functional changes are needed to determine if they can help monitor disease progression and identify asymptomatic individuals at higher risk of clinical deterioration.\n                  <\/jats:p>","DOI":"10.1007\/s12026-026-09826-7","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:33:34Z","timestamp":1787128414000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Spontaneous lymphoproliferation differentiates two groups of HTLV-1 asymptomatic carriers: with and without high cell proliferation and death"],"prefix":"10.1007","volume":"74","author":[{"given":"Marta","family":"de Souza Porto","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Mitiko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Folgosi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dewton","family":"Vasconcelos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Domingues","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Haziot","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jerusa","family":"Smid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Marcusso","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youko","family":"Nukui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Augusto C. P.","family":"Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiane","family":"Assone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jorge","family":"Casseb","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gil","family":"Benard","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"issue":"11","key":"9826_CR1","doi-asserted-by":"publisher","first-page":"5682","DOI":"10.1128\/jvi.64.11.5682-5687.1990","volume":"64","author":"JH Richardson","year":"1990","unstructured":"Richardson JH, Edwards AJ, Cruickshank JK, Rudge P, Dalgleish AG. In vivo cellular tropism of human T-cell leukemia virus type 1. J Virol. 1990;64(11):5682\u20137. https:\/\/doi.org\/10.1128\/jvi.64.11.5682-5687.1990.","journal-title":"J Virol"},{"key":"9826_CR2","first-page":"388","volume":"3","author":"A Gessain","year":"2012","unstructured":"Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol v. 2012;3:388.","journal-title":"Front Microbiol v"},{"issue":"2","key":"9826_CR3","doi-asserted-by":"publisher","first-page":"250","DOI":"10.1002\/ijc.2910430214","volume":"43","author":"EL Murphy","year":"1989","unstructured":"Murphy EL, Hanchard B, Figueroa JP, Gibbs WN, Lofters WS, Campbell M, et al. Modelling the risk of adult T-cell leukemia\/lymphoma in persons infected with human T\u2010lymphotropic virus type I. Int J Cancer. 1989;43(2):250\u20133.","journal-title":"Int J Cancer"},{"issue":"8488","key":"9826_CR4","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/S0140-6736(86)91298-5","volume":"327","author":"M Osame","year":"1986","unstructured":"Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, et al. HTLV-I ASSOCIATED MYELOPATHY, A NEW CLINICAL ENTITY. Lancet. 1986;327(8488):1031\u20132. https:\/\/doi.org\/10.1016\/S0140-6736(86)91298-5.","journal-title":"Lancet"},{"key":"9826_CR5","doi-asserted-by":"publisher","unstructured":"Yamano Y, Sato T. Clinical Pathophysiology of Human T-Lymphotropic Virus-Type 1-Associated Myelopathy\/Tropical Spastic Paraparesis. Front Microbiol. 2012;3. https:\/\/doi.org\/10.3389\/fmicb.2012.00389.","DOI":"10.3389\/fmicb.2012.00389"},{"key":"9826_CR6","doi-asserted-by":"crossref","unstructured":"Tipismana M, Verdonck K, Gonz\u00e1lez E, L\u00f3pez G, Clark D, Gotuzzo E. Subacute progression of HTLV-1 associated myelopathy\/tropical spastic paraparesis in Peru: a report of 20 cases. BMC Proc. dezembro de. 2008;2(S1):P70, 1753-6561-2-s1-p70.","DOI":"10.1186\/1753-6561-2-s1-p70"},{"issue":"5","key":"9826_CR7","doi-asserted-by":"publisher","first-page":"e86144","DOI":"10.1371\/journal.pone.0086144","volume":"9","author":"S Nozuma","year":"2014","unstructured":"Nozuma S, Matsuura E, Matsuzaki T, Watanabe O, Kubota R, Izumo S, et al. Familial clusters of HTLV-1-associated myelopathy\/tropical spastic paraparesis. PLoS ONE. 2014;9(5):e86144.","journal-title":"PLoS ONE"},{"issue":"5","key":"9826_CR8","doi-asserted-by":"publisher","first-page":"e0006967","DOI":"10.1371\/journal.pntd.0006967","volume":"13","author":"ME Haziot","year":"2019","unstructured":"Haziot ME, Gascon MR, Assone T, Fonseca LAM, Luiz ODC, Smid J, et al. Detection of clinical and neurological signs in apparently asymptomatic HTLV-1 infected carriers: Association with high proviral load. Zunt JR, organizador. PLoS Negl Trop Dis. 2019;13(5):e0006967.","journal-title":"PLoS Negl Trop Dis"},{"issue":"3","key":"9826_CR9","doi-asserted-by":"publisher","first-page":"228","DOI":"10.1080\/13550280152403272","volume":"7","author":"T Matsuzaki","year":"2001","unstructured":"Matsuzaki T, Nakagawa M. HTLV-I proviral load correlates with progression of motor disability in HAM\/TSP: Analysis of 239 HAM\/TSP patients including 64 patients followed up for 10 years. J Neurovirol. 2001;7(3):228\u201334. https:\/\/doi.org\/10.1080\/13550280152403272.","journal-title":"J Neurovirol"},{"issue":"3","key":"9826_CR10","doi-asserted-by":"publisher","first-page":"393","DOI":"10.61186\/rbmb.12.3.393","volume":"12","author":"N Ariaee","year":"2023","unstructured":"Ariaee N, Abbasnia S, Sabet F, Mirhossein A, Ahmadi Ghezeldasht S, Moshfegh M, et al. HTLV-1 Proviral Load Absolute RT-qPCR Development for Assessing on Clinical Outcomes in HAM\/TSP Patients. Rep Biochem Mol Biol. 2023;12(3):393\u2013402. https:\/\/doi.org\/10.61186\/rbmb.12.3.393.","journal-title":"Rep Biochem Mol Biol"},{"issue":"1","key":"9826_CR11","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.actatropica.2012.09.012","volume":"125","author":"ALB Starling","year":"2013","unstructured":"Starling ALB, Martins-Filho OA, Lambertucci JR, Labanca L, De Souza Pereira SR, Teixeira-Carvalho A, et al. Proviral load and the balance of serum cytocines in HTLV-1-asymptomatic infection and in HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). Acta Trop. 2013;125(1):75\u201381.","journal-title":"Acta Trop"},{"issue":"8","key":"9826_CR12","doi-asserted-by":"publisher","first-page":"1302","DOI":"10.1212\/WNL.38.8.1302","volume":"38","author":"Y Itoyama","year":"1988","unstructured":"Itoyama Y, Minato S, Kira J, Goto I, Sato H, Okochi K, et al. Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I\u2010associated myelopathy. Neurology. 1988;38(8):1302\u20131302. https:\/\/doi.org\/10.1212\/WNL.38.8.1302.","journal-title":"Neurology"},{"key":"9826_CR13","doi-asserted-by":"publisher","first-page":"326719","DOI":"10.5402\/2011\/326719","volume":"2011","author":"LA Pinto","year":"2011","unstructured":"Pinto LA, Galv\u00e3o Castro B, Soares MBP, Grassi MFR. An Evaluation of the Spontaneous Proliferation of Peripheral Blood Mononuclear Cells in HTLV-1-Infected Individuals Using Flow Cytometry. ISRN Oncol. 2011;2011:326719. https:\/\/doi.org\/10.5402\/2011\/326719.","journal-title":"ISRN Oncol"},{"issue":"1","key":"9826_CR14","doi-asserted-by":"publisher","first-page":"19","DOI":"10.4161\/viru.1.1.9868","volume":"1","author":"PJ Norris","year":"2010","unstructured":"Norris PJ, Hirschkorn DF, DeVita DA, Lee TH, Murphy EL. Human T cell leukemia virus type 1 infection drives spontaneous proliferation of natural killer cells. Virulence. 2010;1(1):19\u201328. https:\/\/doi.org\/10.4161\/viru.1.1.9868.","journal-title":"Virulence"},{"key":"9826_CR15","doi-asserted-by":"publisher","first-page":"831594","DOI":"10.3389\/fmicb.2022.831594","volume":"13","author":"MG Gon\u00e7alves","year":"2022","unstructured":"Gon\u00e7alves MG, Fukasawa LO, Campos KR, Higa FT, Caterino-de-Araujo A. Development and Validation of Multiplex Quantitative Real-Time PCR Assays for Simultaneous Detection and Differentiation of HTLV-1 and HTLV-2, Using Different PCR Platforms and Reagent Brands. Front Microbiol. 2022;13:831594. https:\/\/doi.org\/10.3389\/fmicb.2022.831594.","journal-title":"Front Microbiol"},{"issue":"1","key":"9826_CR16","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/S0166-0934(98)00093-7","volume":"75","author":"JHC Tosswill","year":"1998","unstructured":"Tosswill JHC, Taylor GP, Clewley JP, Weber JN. Quantification of proviral DNA load in human T-cell leukaemia virus type I infections. J Virol Methods. 1998;75(1):21\u20136. https:\/\/doi.org\/10.1016\/S0166-0934(98)00093-7.","journal-title":"J Virol Methods"},{"issue":"5","key":"9826_CR17","doi-asserted-by":"publisher","first-page":"403","DOI":"10.3390\/pathogens13050403","volume":"13","author":"RM Marcusso","year":"2024","unstructured":"Marcusso RM do, Assone N, Haziot T, Smid ME, Folgosi J, Rosadas VA. HTLV-1-Associated Myelopathy (HAM) Incidence in Asymptomatic Carriers and Intermediate Syndrome (IS) Patients. Pathogens. 2024;13(5):403. https:\/\/doi.org\/10.3390\/pathogens13050403.","journal-title":"Pathogens"},{"issue":"2b","key":"9826_CR18","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1590\/S0004-282X2005000300036","volume":"63","author":"CMD Castro-Costa","year":"2005","unstructured":"Castro-Costa CMD, Ara\u00fajo AQC, Menna-Barreto M, Penalva-de-Oliveira AC. Guia de manejo cl\u00ednico do paciente com HTLV: aspectos neurol\u00f3gicos. Arq Neuropsiquiatr. 2005;63(2b):548\u201351. https:\/\/doi.org\/10.1590\/S0004-282X2005000300036.","journal-title":"Arq Neuropsiquiatr"},{"issue":"9","key":"9826_CR19","doi-asserted-by":"publisher","first-page":"2049","DOI":"10.1038\/nprot.2007.296","volume":"2","author":"BJC Quah","year":"2007","unstructured":"Quah BJC, Warren HS, Parish CR. Monitoring lymphocyte proliferation in vitro and in vivo with the intracellular fluorescent dye carboxyfluorescein diacetate succinimidyl ester. Nat Protoc. 2007;2(9):2049\u201356. https:\/\/doi.org\/10.1038\/nprot.2007.296.","journal-title":"Nat Protoc"},{"issue":"9","key":"9826_CR20","doi-asserted-by":"publisher","first-page":"2057","DOI":"10.1038\/nprot.2007.297","volume":"2","author":"ED Hawkins","year":"2007","unstructured":"Hawkins ED, Hommel M, Turner ML, Battye FL, Markham JF, Hodgkin PD. Measuring lymphocyte proliferation, survival and differentiation using CFSE time-series data. Nat Protoc. 2007;2(9):2057\u201367. https:\/\/doi.org\/10.1038\/nprot.2007.297.","journal-title":"Nat Protoc"},{"issue":"1\u20132","key":"9826_CR21","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.jim.2006.04.007","volume":"313","author":"SP Perfetto","year":"2006","unstructured":"Perfetto SP, Chattopadhyay PK, Lamoreaux L, Nguyen R, Ambrozak D, Koup RA, et al. Amine reactive dyes: An effective tool to discriminate live and dead cells in polychromatic flow cytometry. J Immunol Methods. 2006;313(1\u20132):199\u2013208. https:\/\/doi.org\/10.1016\/j.jim.2006.04.007.","journal-title":"J Immunol Methods"},{"issue":"5","key":"9826_CR22","doi-asserted-by":"publisher","first-page":"547","DOI":"10.1128\/CVI.13.5.547-552.2006","volume":"13","author":"RE Mascarenhas","year":"2006","unstructured":"Mascarenhas RE, Brodskyn C, Barbosa G, Clar\u00eancio J, Andrade-Filho AS, Figueiroa F, et al. Peripheral Blood Mononuclear Cells from Individuals Infected with Human T-Cell Lymphotropic Virus Type 1 Have a Reduced Capacity To Respond to Recall Antigens. Clin Vaccine Immunol. 2006;13(5):547\u201352. https:\/\/doi.org\/10.1128\/CVI.13.5.547-552.2006.","journal-title":"Clin Vaccine Immunol"},{"issue":"3","key":"9826_CR23","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1002\/ijc.2910560307","volume":"56","author":"SL Welles","year":"1994","unstructured":"Welles SL, Tachibana N, Okayama A, Shioiri S, Ishihara S, Murai K, et al. Decreased reactivity to PPD among htlv-i carriers in relation to virus and hematologic status. Int J Cancer. 1994;56(3):337\u201340. https:\/\/doi.org\/10.1002\/ijc.2910560307.","journal-title":"Int J Cancer"},{"issue":"2","key":"9826_CR24","doi-asserted-by":"publisher","first-page":"134","DOI":"10.1212\/CPJ.0000000000000866","volume":"11","author":"G Prates","year":"2021","unstructured":"Prates G, Assone T, Corral M, Baldassin MPM, Mitiko T, Silva Sales FC, et al. Prognosis Markers for Monitoring HTLV-1 Neurologic Disease. Neurol Clin Pract. 2021;11(2):134\u201340. https:\/\/doi.org\/10.1212\/CPJ.0000000000000866.","journal-title":"Neurol Clin Pract"},{"issue":"2","key":"9826_CR25","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1016\/j.bjid.2018.02.002","volume":"22","author":"T Assone","year":"2018","unstructured":"Assone T, Kanashiro TM, Baldassin MPM, Paiva A, Haziot ME, Smid J, et al. In vitro basal T-cell proliferation among asymptomatic Human T cell Leukemia Virus type 1 patients co-infected with hepatitis C and\/or Human Immunodeficiency Virus type 1. Braz J Infect Dis. 2018;22(2):106\u201312. https:\/\/doi.org\/10.1016\/j.bjid.2018.02.002.","journal-title":"Braz J Infect Dis"},{"issue":"1","key":"9826_CR26","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/1471-2334-4-7","volume":"4","author":"SB Santos","year":"2004","unstructured":"Santos SB, Porto AF, Muniz AL, De Jesus AR, Magalh\u00e3es E, Melo A, et al. Exacerbated inflammatory cellular immune response characteristics of HAM\/TSP is observed in a large proportion of HTLV-I asymptomatic carriers. BMC Infect Dis. 2004;4(1):7. https:\/\/doi.org\/10.1186\/1471-2334-4-7.","journal-title":"BMC Infect Dis"},{"issue":"4","key":"9826_CR27","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1093\/glycob\/cwu004","volume":"24","author":"M Nagae","year":"2014","unstructured":"Nagae M, Soga K, Morita-Matsumoto K, Hanashima S, Ikeda A, Yamamoto K, et al. Phytohemagglutinin from Phaseolus vulgaris (PHA-E) displays a novel glycan recognition mode using a common legume lectin fold. Glycobiology. 2014;24(4):368\u201378. https:\/\/doi.org\/10.1093\/glycob\/cwu004.","journal-title":"Glycobiology"},{"issue":"2","key":"9826_CR28","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1016\/0014-4827(71)90006-1","volume":"65","author":"K Lindahlkiessling","year":"1971","unstructured":"Lindahlkiessling K, Mattsson A. Mechanism of phytohemagglutinin (PHA) action IV. Effect of some metabolic inhibitors on binding of PHA to lymphocytes and the stimulatory potential of PHA-pretreated cells. Exp Cell Res. 1971;65(2):307\u201312. https:\/\/doi.org\/10.1016\/0014-4827(71)90006-1.","journal-title":"Exp Cell Res"},{"issue":"6","key":"9826_CR29","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1016\/S0198-8859(98)00029-9","volume":"59","author":"R Rabinowitz","year":"1998","unstructured":"Rabinowitz R, Pokroy R, Yu Y, Schlesinger M, Activated Human T-C, Bestow. T-Cell Antigens to Non-T-Cells by Intercellular Antigen Transfer. Hum Immunol. 1998;59(6):331\u201342. https:\/\/doi.org\/10.1016\/S0198-8859(98)00029-9.","journal-title":"Hum Immunol"},{"issue":"1\u20132","key":"9826_CR30","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1016\/j.jim.2004.07.006","volume":"293","author":"M Reddy","year":"2004","unstructured":"Reddy M, Eirikis E, Davis C, Davis HM, Prabhakar U. Comparative analysis of lymphocyte activation marker expression and cytokine secretion profile in stimulated human peripheral blood mononuclear cell cultures: an in vitro model to monitor cellular immune function. J Immunol Methods. 2004;293(1\u20132):127\u201342. https:\/\/doi.org\/10.1016\/j.jim.2004.07.006.","journal-title":"J Immunol Methods"},{"issue":"20","key":"9826_CR31","doi-asserted-by":"publisher","first-page":"1359","DOI":"10.1038\/sj.gt.3301807","volume":"9","author":"RF Duarte","year":"2002","unstructured":"Duarte RF, Chen FE, Lowdell MW, Potter MN, Lamana ML, Prentice HG, et al. Functional impairment of human T-lymphocytes following PHA-induced expansion and retroviral transduction: implications for gene therapy. Gene Ther. 2002;9(20):1359\u201368. https:\/\/doi.org\/10.1038\/sj.gt.3301807.","journal-title":"Gene Ther"},{"issue":"12","key":"9826_CR32","doi-asserted-by":"publisher","first-page":"3758","DOI":"10.4049\/jimmunol.137.12.3758","volume":"137","author":"L Davis","year":"1986","unstructured":"Davis L, Vida R, Lipsky PE. Regulation of human T lymphocyte mitogenesis by antibodies to CD3. J Immunoll. 1986;137(12):3758\u201367. https:\/\/doi.org\/10.4049\/jimmunol.137.12.3758.","journal-title":"J Immunoll"},{"issue":"2","key":"9826_CR33","doi-asserted-by":"publisher","first-page":"1271","DOI":"10.1128\/JVI.73.2.1271-1277.1999","volume":"73","author":"Y Iwanaga","year":"1999","unstructured":"Iwanaga Y, Tsukahara T, Ohashi T, Tanaka Y, Arai M, Nakamura M, et al. Human T-Cell Leukemia Virus Type 1 Tax Protein Abrogates Interleukin-2 Dependence in a Mouse T-Cell Line. J Virol. 1999;73(2):1271\u20137. https:\/\/doi.org\/10.1128\/JVI.73.2.1271-1277.1999.","journal-title":"J Virol"},{"issue":"1","key":"9826_CR34","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1038\/s41408-023-00841-7","volume":"13","author":"R Hleihel","year":"2023","unstructured":"Hleihel R, Skayneh H, De Th\u00e9 H, Hermine O, Bazarbachi A. Primary cells from patients with adult T cell leukemia\/lymphoma depend on HTLV-1 Tax expression for NF-\u03baB activation and survival. Blood Cancer J. 2023;13(1):67. https:\/\/doi.org\/10.1038\/s41408-023-00841-7.","journal-title":"Blood Cancer J"},{"issue":"4","key":"9826_CR35","doi-asserted-by":"publisher","first-page":"e1002025","DOI":"10.1371\/journal.ppat.1002025","volume":"7","author":"H Zhi","year":"2011","unstructured":"Zhi H, Yang L, Kuo YL, Ho YK, Shih HM, Giam CZ. NF-\u03baB Hyper-Activation by HTLV-1 Tax Induces Cellular Senescence, but Can Be Alleviated by the Viral Anti-Sense Protein HBZ. Emerman M, organizador. PLoS Pathog. 2011;7(4):e1002025. https:\/\/doi.org\/10.1371\/journal.ppat.1002025.","journal-title":"PLoS Pathog"},{"issue":"2","key":"9826_CR36","doi-asserted-by":"publisher","first-page":"113","DOI":"10.1046\/j.1423-0410.1998.7420113.x","volume":"74","author":"M Mincheff","year":"1998","unstructured":"Mincheff M, Loukinov D, Zoubak S, Hammett M, Meryman H. Fas and Fas Ligand Expression on Human Peripheral Blood Leukocytes. Vox Sang. 1998;74(2):113\u201321. https:\/\/doi.org\/10.1046\/j.1423-0410.1998.7420113.x.","journal-title":"Vox Sang"},{"issue":"6","key":"9826_CR37","doi-asserted-by":"publisher","first-page":"736","DOI":"10.1128\/cdli.4.6.736-741.1997","volume":"4","author":"AH Patki","year":"1997","unstructured":"Patki AH, Georges DL, Lederman MM. CD4+-T-cell counts, spontaneous apoptosis, and Fas expression in peripheral blood mononuclear cells obtained from human immunodeficiency virus type 1-infected subjects. Clin Diagn Lab Immunol. 1997;4(6):736\u201341. https:\/\/doi.org\/10.1128\/cdli.4.6.736-741.1997.","journal-title":"Clin Diagn Lab Immunol"},{"issue":"4","key":"9826_CR38","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1016\/j.ymeth.2010.01.027","volume":"50","author":"M Alunni-Fabbroni","year":"2010","unstructured":"Alunni-Fabbroni M, Sandri MT. Circulating tumour cells in clinical practice: Methods of detection and possible characterization. Methods. 2010;50(4):289\u201397. https:\/\/doi.org\/10.1016\/j.ymeth.2010.01.027.","journal-title":"Methods"},{"issue":"2","key":"9826_CR39","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1046\/j.1365-2249.2000.01211.x","volume":"120","author":"Y Furukawa","year":"2001","unstructured":"Furukawa Y, Bangham CRM, Taylor GP, Weber JN, Osame M. Frequent reversible membrane damage in peripheral blood B cells in human T cell lymphotropic virus type I (HTLV-I)-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). Clin Exp Immunol. 2001;120(2):307\u201316. https:\/\/doi.org\/10.1046\/j.1365-2249.2000.01211.x.","journal-title":"Clin Exp Immunol"},{"issue":"2","key":"9826_CR40","doi-asserted-by":"publisher","first-page":"169","DOI":"10.1006\/clim.2001.5101","volume":"101","author":"AM Dyrhol-Riise","year":"2001","unstructured":"Dyrhol-Riise AM, Stent G, R\u00f8sok BI, Voltersvik P, Olofsson J, \u00c5sj\u00f6 B. The Fas\/FasL System and T Cell Apoptosis in HIV-1-Infected Lymphoid Tissue during Highly Active Antiretroviral Therapy. Clin Immunol. 2001;101(2):169\u201379. https:\/\/doi.org\/10.1006\/clim.2001.5101.","journal-title":"Clin Immunol"},{"issue":"1","key":"9826_CR41","doi-asserted-by":"publisher","first-page":"7785","DOI":"10.1038\/s41598-017-08578-7","volume":"7","author":"A Malyshkina","year":"2017","unstructured":"Malyshkina A, Littwitz-Salomon E, Sutter K, Zelinskyy G, Windmann S, Schimmer S, et al. Fas Ligand-mediated cytotoxicity of CD4\u2009+\u2009T cells during chronic retrovirus infection. Sci Rep. 2017;7(1):7785. https:\/\/doi.org\/10.1038\/s41598-017-08578-7.","journal-title":"Sci Rep"},{"issue":"12","key":"9826_CR42","doi-asserted-by":"publisher","first-page":"3277","DOI":"10.1099\/0022-1317-78-12-3277","volume":"78","author":"X Chen","year":"1997","unstructured":"Chen X, Liu X, Zdravkovic M, Guo M, Zachar V, Ebbesen P. Role of the Fas\/Fas ligand pathway in apoptotic cell death induced by the human T cell lymphotropic virus type I Tax transactivator. J Gen Virol. 1997;78(12):3277\u201385.","journal-title":"J Gen Virol"},{"issue":"6","key":"9826_CR43","doi-asserted-by":"publisher","first-page":"1017","DOI":"10.1084\/jem.191.6.1017","volume":"191","author":"J Zhang","year":"2000","unstructured":"Zhang J, Gao JX, Salojin K, Shao Q, Grattan M, Meagher C, et al. Regulation of fas ligand expression during activation-induced cell death in T cells by p38 mitogen-activated protein kinase and c-Jun NH2-terminal kinase. J Exp Med. 2000;191(6):1017\u201330. https:\/\/doi.org\/10.1084\/jem.191.6.1017.","journal-title":"J Exp Med"},{"issue":"3","key":"9826_CR44","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1016\/S1044-5323(03)00035-6","volume":"15","author":"T Brunner","year":"2003","unstructured":"Brunner T. Fas (CD95\/Apo-1) ligand regulation in T cell homeostasis, cell-mediated cytotoxicity and immune pathology. Semin Immunoll. 2003;15(3):167\u201376. https:\/\/doi.org\/10.1016\/S1044-5323(03)00035-6.","journal-title":"Semin Immunoll"},{"issue":"1","key":"9826_CR45","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1038\/cr.2009.112","volume":"20","author":"PD Arkwright","year":"2010","unstructured":"Arkwright PD, Luchetti F, Tour J, Roberts C, Ayub R, Morales AP, et al. Fas stimulation of T lymphocytes promotes rapid intercellular exchange of death signals via membrane nanotubes. Cell Res. 2010;20(1):72\u201388. https:\/\/doi.org\/10.1038\/cr.2009.112.","journal-title":"Cell Res"},{"issue":"5","key":"9826_CR46","doi-asserted-by":"publisher","first-page":"e1741","DOI":"10.1038\/cddis.2015.100","volume":"6","author":"MT Cencioni","year":"2015","unstructured":"Cencioni MT, Santini S, Ruocco G, Borsellino G, De Bardi M, Grasso MG, et al. FAS-ligand regulates differential activation-induced cell death of human T-helper 1 and 17 cells in healthy donors and multiple sclerosis patients. Cell Death Dis. 2015;6(5):e1741\u20131741. https:\/\/doi.org\/10.1038\/cddis.2015.100.","journal-title":"Cell Death Dis"},{"issue":"10","key":"9826_CR47","doi-asserted-by":"publisher","first-page":"e13703","DOI":"10.1111\/acel.13703","volume":"21","author":"A Cevirgel","year":"2022","unstructured":"Cevirgel A, Shetty SA, Vos M, Nanlohy NM, Beckers L, Bijvank E, et al. Identification of aging-associated immunotypes and immune stability as indicators of post\u2010vaccination immune activation. Aging Cell. 2022;21(10):e13703. https:\/\/doi.org\/10.1111\/acel.13703.","journal-title":"Aging Cell"},{"issue":"10","key":"9826_CR48","doi-asserted-by":"publisher","first-page":"2756","DOI":"10.1002\/acn3.52190","volume":"11","author":"A Lv","year":"2024","unstructured":"Lv A, Fang Y, Lin X, Chen J, Song H, Wang N, et al. B-cell depletion limits HTLV\u20101\u2010infected T\u2010cell expansion and ameliorate HTLV\u20101\u2010associated myelopathy. Ann Clin Transl Neurol. 2024;11(10):2756\u201368. https:\/\/doi.org\/10.1002\/acn3.52190.","journal-title":"Ann Clin Transl Neurol"},{"issue":"1","key":"9826_CR49","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1097\/00042560-199909010-00012","volume":"22","author":"GP Taylor","year":"1999","unstructured":"Taylor GP, Tosswill JHC, Matutes E, Daenke S, Hall S, Bain BJ, et al. Prospective Study of HTLV-I Infection in an Initially Asymptomatic Cohort. J Acquir Immune Defic Syndr. 1999;22(1):92. https:\/\/doi.org\/10.1097\/00042560-199909010-00012.","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"S1","key":"9826_CR50","doi-asserted-by":"publisher","first-page":"P16","DOI":"10.1186\/1742-4690-11-S1-P16","volume":"11","author":"R Okajima","year":"2014","unstructured":"Okajima R, Smid J, Duarte AJ, De Oliveira ACP, Casseb J, Sanches JA Junior. Correlation of HTLV-1 proviral load and lymphocyte proliferation from asymptomatic HTLV-1-positive patients and HAM\/TSP patients associated or not to skin disorders. Retrovirology. 2014;11(S1):P16\u20131742.","journal-title":"Retrovirology"},{"issue":"2","key":"9826_CR51","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1089\/aid.2012.0132","volume":"29","author":"MA Demontis","year":"2013","unstructured":"Demontis MA, Hilburn S, Taylor GP, Human T. Cell Lymphotropic Virus Type 1 Viral Load Variability and Long-Term Trends in Asymptomatic Carriers and in Patients with Human T Cell Lymphotropic Virus Type 1-Related Diseases. AIDS Res Hum Retroviruses. 2013;29(2):359\u201364. https:\/\/doi.org\/10.1089\/aid.2012.0132.","journal-title":"AIDS Res Hum Retroviruses"},{"issue":"4","key":"9826_CR52","doi-asserted-by":"publisher","first-page":"520","DOI":"10.1007\/s13365-020-00847-y","volume":"26","author":"SN Ferraz","year":"2020","unstructured":"Ferraz SN, Costa GF, Carneiro Neto JA, Hebert T, De Oliveira CJV, Guerra M, et al. Neurologic, clinical, and immunologic features in a cohort of HTLV-1 carriers with high proviral loads. J Neurovirol. 2020;26(4):520\u20139. https:\/\/doi.org\/10.1007\/s13365-020-00847-y.","journal-title":"J Neurovirol"},{"issue":"44","key":"9826_CR53","doi-asserted-by":"publisher","first-page":"e2308511120","DOI":"10.1073\/pnas.2308511120","volume":"120","author":"R Sender","year":"2023","unstructured":"Sender R, Weiss Y, Navon Y, Milo I, Azulay N, Keren L, et al. The total mass, number, and distribution of immune cells in the human body. Proc Natl Acad Sci. 2023;120(44):e2308511120. https:\/\/doi.org\/10.1073\/pnas.2308511120.","journal-title":"Proc Natl Acad Sci"},{"key":"9826_CR54","doi-asserted-by":"publisher","first-page":"1653384","DOI":"10.3389\/fmed.2025.1653384","volume":"12","author":"S Shegefti","year":"2025","unstructured":"Shegefti S, Alaei M, Ghahari N, Telittchenko R, Hanafi SB, Isnard S, et al. Sustained inflammation during human T-lymphotropic virus type 1 infection: a wildfire contributing to disease progression. Front Med. 2025;12:1653384. https:\/\/doi.org\/10.3389\/fmed.2025.1653384.","journal-title":"Front Med"},{"key":"9826_CR55","doi-asserted-by":"publisher","first-page":"867478","DOI":"10.3389\/fmed.2022.867478","volume":"9","author":"M Miura","year":"2022","unstructured":"Miura M, Naito T, Saito M. Current Perspectives in Human T-Cell Leukemia Virus Type 1 Infection and Its Associated Diseases. Front Med. 2022;9:867478. https:\/\/doi.org\/10.3389\/fmed.2022.867478.","journal-title":"Front Med"},{"issue":"19","key":"9826_CR56","doi-asserted-by":"publisher","first-page":"8035","DOI":"10.1073\/pnas.0608832104","volume":"104","author":"B Asquith","year":"2007","unstructured":"Asquith B, Zhang Y, Mosley AJ, De Lara CM, Wallace DL, Worth A, et al. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc Natl Acad Sci. 2007;104(19):8035\u201340. https:\/\/doi.org\/10.1073\/pnas.0608832104.","journal-title":"Proc Natl Acad Sci"}],"container-title":["Immunologic Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09826-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12026-026-09826-7","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12026-026-09826-7.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T08:33:37Z","timestamp":1787128417000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12026-026-09826-7"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,19]]},"references-count":56,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["9826"],"URL":"https:\/\/doi.org\/10.1007\/s12026-026-09826-7","relation":{},"ISSN":["1559-0755"],"issn-type":[{"value":"1559-0755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,19]]},"assertion":[{"value":"5 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"12 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"19 August 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Declarations"}}],"article-number":"90"}}