{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,12]],"date-time":"2026-04-12T18:31:02Z","timestamp":1776018662342,"version":"3.50.1"},"reference-count":105,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T00:00:00Z","timestamp":1715558400000},"content-version":"vor","delay-in-days":133,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP19H05426"],"award-info":[{"award-number":["JP19H05426"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21K07082"],"award-info":[{"award-number":["JP21K07082"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["JP21H00433"],"award-info":[{"award-number":["JP21H00433"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,1,1]]},"abstract":"<jats:title>Summary<\/jats:title>\n               <jats:p>Despite extensive regulatory T cell (Treg) research, fundamental questions on in vivo dynamics remain to be answered. The current study aims to dissect several interwoven concepts in Treg biology, highlighting the \u2018self-reactivity\u2019 of Treg and their counterparts, namely naturally-arising memory-phenotype T-cells, as a key mechanism to be exploited by a human retroviral infection. We propose the novel key concept, Periodic T cell receptor (TCR)-signalled T-cells, capturing self-reactivity in a quantifiable manner using the Nr4a3-Timer-of-cell-kinetics-and-activity (Tocky) technology. Periodic and brief TCR signals in self-reactive T-cells contrast with acute TCR signals during inflammation. Thus, we propose a new two-axis model for T-cell activation by the two types of TCR signals or antigen recognition, elucidating how Foxp3 expression and acute TCR signals actively regulate Periodic TCR-signalled T-cells. Next, we highlight an underappreciated branch of immunological research on Human T-cell Leukemia Virus type 1 (HTLV-1) that precedes Treg studies, illuminating the missing link between the viral infection, CD25, and Foxp3. Based on evidence by single-cell analysis, we show how the viral infection exploits the regulatory mechanisms for T-cell activation and suggests a potential role of periodic TCR signalling in infection and malignant transformation. In conclusion, the new perspectives and models in this study provide a working framework for investigating Treg within the self-reactive T-cell spectrum, expected to advance understanding of HTLV-1 infection, cancer, and immunotherapy strategies for these conditions.<\/jats:p>","DOI":"10.1093\/discim\/kyae006","type":"journal-article","created":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T06:24:51Z","timestamp":1715581491000},"source":"Crossref","is-referenced-by-count":7,"title":["Spectrum of Treg and self-reactive T cells: single cell perspectives from old friend HTLV-1"],"prefix":"10.1093","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9284-7326","authenticated-orcid":false,"given":"Masahiro","family":"Ono","sequence":"first","affiliation":[{"name":"Department of Life Sciences, Imperial College London , London , United Kingdom"},{"name":"Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1495-7810","authenticated-orcid":false,"given":"Yorifumi","family":"Satou","sequence":"additional","affiliation":[{"name":"Joint Research Center for Human Retrovirus Infection, Kumamoto University , Kumamoto , Japan"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2024,5,13]]},"reference":[{"key":"2024061111491812400_CIT0001","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/j.cell.2008.05.009","article-title":"Regulatory T cells and immune tolerance","volume":"133","author":"Sakaguchi","year":"2008","journal-title":"Cell"},{"key":"2024061111491812400_CIT0002","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1146\/annurev.immunol.25.022106.141623","article-title":"Regulatory T cells: mechanisms of differentiation and function","volume":"30","author":"Josefowicz","year":"2012","journal-title":"Annu Rev Immunol"},{"key":"2024061111491812400_CIT0003","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1111\/imr.12178","article-title":"Regulatory cells in health and disease","volume":"259","author":"Caton","year":"2014","journal-title":"Immunol Rev"},{"key":"2024061111491812400_CIT0004","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1038\/nri3667","article-title":"Positive and negative selection of the T cell repertoire: what thymocytes see (and don\u2019t see)","volume":"14","author":"Klein","year":"2014","journal-title":"Nat Rev Immunol"},{"key":"2024061111491812400_CIT0005","doi-asserted-by":"crossref","first-page":"2931","DOI":"10.1083\/jcb.201711048","article-title":"A timer for analyzing temporally dynamic changes in transcription during differentiation in vivo","volume":"217","author":"Bending","year":"2018","journal-title":"J Cell Biol"},{"key":"2024061111491812400_CIT0006","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.immuni.2014.10.012","article-title":"Continuous T cell receptor signals maintain a functional regulatory T cell pool","volume":"41","author":"Vahl","year":"2014","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0007","doi-asserted-by":"crossref","first-page":"1070","DOI":"10.1038\/ni.3004","article-title":"Continuous requirement for the TCR in regulatory T cell function","volume":"15","author":"Levine","year":"2014","journal-title":"Nat Immunol"},{"key":"2024061111491812400_CIT0008","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1111\/imr.12165","article-title":"Homeostasis and function of regulatory T cells (Tregs) in vivo: lessons from TCR-transgenic Tregs","volume":"259","author":"Attridge","year":"2014","journal-title":"Immunol Rev"},{"key":"2024061111491812400_CIT0009","doi-asserted-by":"crossref","first-page":"eaaf7471","DOI":"10.1126\/sciimmunol.aaf7471","article-title":"Tissue-specific emergence of regulatory and intraepithelial T cells from a clonal T cell precursor","volume":"1","author":"Bilate","year":"2016","journal-title":"Sci Immunol"},{"key":"2024061111491812400_CIT0010","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.1126\/science.aaf3892","article-title":"Tissue adaptation of regulatory and intraepithelial CD4+ T cells controls gut inflammation","volume":"352","author":"Sujino","year":"2016","journal-title":"Science"},{"key":"2024061111491812400_CIT0011","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1016\/j.coi.2012.04.009","article-title":"T cell tolerance and immunity to commensal bacteria","volume":"24","author":"Nutsch","year":"2012","journal-title":"Curr Opin Immunol"},{"key":"2024061111491812400_CIT0012","doi-asserted-by":"crossref","first-page":"5300","DOI":"10.4049\/jimmunol.157.12.5300","article-title":"Memory T cell development in the absence of specific antigen priming","volume":"157","author":"Lee","year":"1996","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0013","doi-asserted-by":"crossref","first-page":"3752","DOI":"10.4049\/jimmunol.169.7.3752","article-title":"TCR and IL-7 receptor signals can operate independently or synergize to promote lymphopenia-induced expansion of naive T cells","volume":"169","author":"Seddon","year":"2002","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0014","doi-asserted-by":"crossref","first-page":"7259","DOI":"10.4049\/jimmunol.173.12.7259","article-title":"CD25- T cells generate CD25+FOXP3+ regulatory T cells by peripheral expansion","volume":"173","author":"Curotto de Lafaille","year":"2004","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0015","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.immuni.2011.12.012","article-title":"Plasticity of FOXP3(+) T cells reflects promiscuous FOXP3 expression in conventional T cells but not reprogramming of regulatory T cells","volume":"36","author":"Miyao","year":"2012","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0016","doi-asserted-by":"crossref","first-page":"2209","DOI":"10.1038\/ncomms3209","article-title":"Highly self-reactive naive CD4 T cells are prone to differentiate into regulatory T cells","volume":"4","author":"Martin","year":"2013","journal-title":"Nat Commun"},{"key":"2024061111491812400_CIT0017","doi-asserted-by":"crossref","first-page":"eaam9304","DOI":"10.1126\/sciimmunol.aam9304","article-title":"Memory-phenotype CD4(+) T cells spontaneously generated under steady-state conditions exert innate t(h)1-like effector function","volume":"2","author":"Kawabe","year":"2017","journal-title":"Sci Immunol"},{"key":"2024061111491812400_CIT0018","doi-asserted-by":"crossref","first-page":"4748","DOI":"10.4049\/jimmunol.176.8.4748","article-title":"Control of autoimmune myocarditis and multiorgan inflammation by glucocorticoid-induced tnf receptor family-related protein(high), FOXP3-expressing CD25+ and CD25-regulatory T cells","volume":"176","author":"Ono","year":"2006","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0019","doi-asserted-by":"crossref","first-page":"eabo5558","DOI":"10.1126\/sciimmunol.abo5558","article-title":"Acquisition of suppressive function by conventional T cells limits antitumor immunity upon t(reg) depletion","volume":"8","author":"Whiteside","year":"2023","journal-title":"Sci Immunol"},{"key":"2024061111491812400_CIT0020","doi-asserted-by":"crossref","first-page":"672","DOI":"10.4049\/jimmunol.170.2.672","article-title":"Cutting edge: Homeostatic proliferation of peripheral T lymphocytes is regulated by clonal competition","volume":"170","author":"Troy","year":"2003","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0021","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/S0952-7915(03)00049-9","article-title":"Regulation of peripheral T-cell homeostasis by receptor signalling","volume":"15","author":"Seddon","year":"2003","journal-title":"Curr Opin Immunol"},{"key":"2024061111491812400_CIT0022","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1038\/icb.2015.65","article-title":"Controversies concerning thymus-derived regulatory T cells: fundamental issues and a new perspective","volume":"94","author":"Ono","year":"2016","journal-title":"Immunol Cell Biol"},{"key":"2024061111491812400_CIT0023","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1016\/S1074-7613(00)80055-2","article-title":"Designing and maintaining the mature tcr repertoire: the continuum of self-peptide:Self-MHC complex recognition","volume":"10","author":"Viret","year":"1999","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0024","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nature01146","article-title":"Self-recognition promotes the foreign antigen sensitivity of naive T lymphocytes","volume":"420","author":"Stefanov\u00e1","year":"2002","journal-title":"Nature"},{"key":"2024061111491812400_CIT0025","doi-asserted-by":"crossref","first-page":"2997","DOI":"10.4049\/jimmunol.169.6.2997","article-title":"TCR signals mediated by Src family kinases are essential for the survival of naive T cells","volume":"169","author":"Seddon","year":"2002","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0026","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1038\/ni.2822","article-title":"Intrinsic CD4+ T cell sensitivity and response to a pathogen are set and sustained by avidity for thymic and peripheral complexes of self peptide and MHC","volume":"15","author":"Persaud","year":"2014","journal-title":"Nat Immunol"},{"key":"2024061111491812400_CIT0027","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1038\/nchembio.138","article-title":"Monomeric fluorescent timers that change color from blue to red report on cellular trafficking","volume":"5","author":"Subach","year":"2009","journal-title":"Nat Chem Biol"},{"key":"2024061111491812400_CIT0028","doi-asserted-by":"crossref","first-page":"e99013","DOI":"10.15252\/embj.201899013","article-title":"A temporally dynamic FOXP3 autoregulatory transcriptional circuit controls the effector Treg programme","volume":"37","author":"Bending","year":"2018","journal-title":"EMBO J"},{"key":"2024061111491812400_CIT0029","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1084\/jem.20050784","article-title":"Developmental regulation of FOXP3 expression during ontogeny","volume":"202","author":"Fontenot","year":"2005","journal-title":"J Exp Med"},{"key":"2024061111491812400_CIT0030","doi-asserted-by":"crossref","first-page":"4366","DOI":"10.4049\/jimmunol.180.7.4366","article-title":"Cutting edge: autoimmune disease in day 3 thymectomized mice is actively controlled by endogenous disease-specific regulatory T cells","volume":"180","author":"Samy","year":"2008","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0031","doi-asserted-by":"crossref","first-page":"949","DOI":"10.1016\/j.immuni.2013.10.016","article-title":"Self-antigen-driven activation induces instability of regulatory T cells during an inflammatory autoimmune response","volume":"39","author":"Bailey-Bucktrout","year":"2013","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0032","doi-asserted-by":"crossref","first-page":"2080","DOI":"10.1111\/cas.14069","article-title":"Regulatory T (Treg) cells in cancer: can Treg cells be a new therapeutic target","volume":"110","author":"Ohue","year":"2019","journal-title":"Cancer Sci"},{"key":"2024061111491812400_CIT0033","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nri.2016.26","article-title":"T cell receptor signalling in the control of regulatory T cell differentiation and function","volume":"16","author":"Li","year":"2016","journal-title":"Nat Rev Immunol"},{"key":"2024061111491812400_CIT0034","doi-asserted-by":"crossref","first-page":"8449","DOI":"10.1038\/s41467-023-44297-6","article-title":"Antigen recognition reinforces regulatory T cell mediated leishmania major persistence","volume":"14","author":"Zayats","year":"2023","journal-title":"Nat Commun"},{"key":"2024061111491812400_CIT0035","doi-asserted-by":"crossref","first-page":"25","DOI":"10.12703\/r\/12-25","article-title":"Recent advances in understanding TCR signaling: a synaptic perspective","volume":"12","author":"Dustin","year":"2023","journal-title":"Fac Rev"},{"key":"2024061111491812400_CIT0036","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.4049\/jimmunol.0803827","article-title":"Analysis of adhesion molecules, target cells, and role of IL-2 in human FOXP3+ regulatory T cell suppressor function","volume":"182","author":"Tran","year":"2009","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0037","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1002\/ijc.25902","article-title":"CD103 is a hallmark of tumor-infiltrating regulatory T cells","volume":"129","author":"Anz","year":"2011","journal-title":"Int J Cancer"},{"key":"2024061111491812400_CIT0038","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1111\/imm.13178","article-title":"Control of regulatory T-cell differentiation and function by T-cell receptor signalling and FOXP3 transcription factor complexes","volume":"160","author":"Ono","year":"2020","journal-title":"Immunology"},{"key":"2024061111491812400_CIT0039","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.immuni.2009.03.019","article-title":"Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FOXP3 transcription factor","volume":"30","author":"Miyara","year":"2009","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0040","doi-asserted-by":"crossref","first-page":"2885","DOI":"10.4049\/jimmunol.1402695","article-title":"Regulatory T cells in melanoma revisited by a computational clustering of FOXP3+ T cell subpopulations","volume":"196","author":"Fujii","year":"2016","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0041","doi-asserted-by":"crossref","first-page":"7713","DOI":"10.4049\/jimmunol.181.11.7713","article-title":"An in vitro system to model the establishment and reactivation of HIV-1 latency","volume":"181","author":"Marini","year":"2008","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0042","doi-asserted-by":"crossref","first-page":"7698","DOI":"10.4049\/jimmunol.177.11.7698","article-title":"Control of memory CD4 T cell recall by the CD28\/B7 costimulatory pathway","volume":"177","author":"Ndejembi","year":"2006","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0043","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases","volume":"24","author":"Proietti","year":"2005","journal-title":"Oncogene"},{"key":"2024061111491812400_CIT0044","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1182\/blood.V50.3.481.481","article-title":"Adult T-cell leukemia: clinical and hematologic features of 16 cases","volume":"50","author":"Uchiyama","year":"1977","journal-title":"Blood"},{"key":"2024061111491812400_CIT0045","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","article-title":"Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis","volume":"2","author":"Gessain","year":"1985","journal-title":"Lancet"},{"key":"2024061111491812400_CIT0046","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(86)91298-5","article-title":"HTLV-I associated myelopathy, a new clinical entity","volume":"1","author":"Osame","year":"1986","journal-title":"Lancet"},{"key":"2024061111491812400_CIT0047","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1038\/311631a0","article-title":"Molecular cloning of cdna encoding human interleukin-2 receptor","volume":"311","author":"Nikaido","year":"1984","journal-title":"Nature"},{"key":"2024061111491812400_CIT0048","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1038\/311626a0","article-title":"Molecular cloning and expression of cdnas for the human interleukin-2 receptor","volume":"311","author":"Leonard","year":"1984","journal-title":"Nature"},{"key":"2024061111491812400_CIT0049","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/1074-7613(95)90180-9","article-title":"Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment","volume":"3","author":"Willerford","year":"1995","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0050","doi-asserted-by":"crossref","first-page":"1151","DOI":"10.4049\/jimmunol.155.3.1151","article-title":"Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases","volume":"155","author":"Sakaguchi","year":"1995","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0051","doi-asserted-by":"crossref","first-page":"1245","DOI":"10.4049\/jimmunol.167.3.1245","article-title":"Cd4+CD25 high regulatory cells in human peripheral blood","volume":"167","author":"Baecher-Allan","year":"2001","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0052","doi-asserted-by":"crossref","first-page":"4622","DOI":"10.4049\/jimmunol.176.8.4622","article-title":"MHC class II expression identifies functionally distinct human regulatory T cells 1","volume":"176","author":"Baecher-Allan","year":"2006","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0053","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1084\/jem.20060772","article-title":"Cd127 expression inversely correlates with FOXP3 and suppressive function of human CD4+ t reg cells","volume":"203","author":"Liu","year":"2006","journal-title":"J Exp Med"},{"key":"2024061111491812400_CIT0054","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1172\/JCI111992","article-title":"Interleukin-2 receptor (tac antigen) expressed on adult T cell leukemia cells","volume":"76","author":"Uchiyama","year":"1985","journal-title":"J Clin Invest"},{"key":"2024061111491812400_CIT0055","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1186\/1742-4690-9-46","article-title":"HTLV-1 modulates the frequency and phenotype of FOXP3+CD4+T cells in virus-infected individuals","volume":"9","author":"Satou","year":"2012","journal-title":"Retrovirology"},{"key":"2024061111491812400_CIT0056","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1111\/j.1365-2141.2004.04999.x","article-title":"Expression of FOXP3, a key molecule in CD4+CD25+ regulatory T cells, in adult t-cell leukaemia\/lymphoma cells","volume":"126","author":"Karube","year":"2004","journal-title":"Br J Haematol"},{"key":"2024061111491812400_CIT0057","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1093\/intimm\/dxh366","article-title":"Regulatory T cell-like activity of FOXP3+ adult T cell leukemia cells","volume":"18","author":"Chen","year":"2006","journal-title":"Int Immunol"},{"key":"2024061111491812400_CIT0058","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1111\/j.1349-7006.2007.00646.x","article-title":"Adult T-cell leukemia\/lymphoma cells from blood and skin tumors express cytotoxic t lymphocyte-associated antigen-4 and FOXP3 but lack suppressor activity toward autologous cd8+ T cells","volume":"99","author":"Shimauchi","year":"2008","journal-title":"Cancer Sci"},{"key":"2024061111491812400_CIT0059","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1111\/j.1600-0609.2008.01105.x","article-title":"Foxp3 expression on normal and leukemic CD4+CD25+ T cells implicated in human T-cell leukemia virus type-1 is inconsistent with Treg cells","volume":"81","author":"Abe","year":"2008","journal-title":"Eur J Haematol"},{"key":"2024061111491812400_CIT0060","doi-asserted-by":"crossref","first-page":"e20616","DOI":"10.7554\/eLife.20616","article-title":"Adequate immune response ensured by binary IL-2 and graded CD25 expression in a murine transfer model","volume":"5","author":"Fuhrmann","year":"2016","journal-title":"eLife"},{"key":"2024061111491812400_CIT0061","doi-asserted-by":"crossref","first-page":"2994","DOI":"10.1182\/blood-2009-07-231050","article-title":"Immune activation induces immortalization of HTLV-1 LTR-Tax transgenic CD4+ T cells","volume":"116","author":"Swaims","year":"2010","journal-title":"Blood"},{"key":"2024061111491812400_CIT0062","doi-asserted-by":"crossref","first-page":"e1001274","DOI":"10.1371\/journal.ppat.1001274","article-title":"HTLV-1 bzip factor induces T-cell lymphoma and systemic inflammation in vivo","volume":"7","author":"Satou","year":"2011","journal-title":"PLoS Pathog"},{"key":"2024061111491812400_CIT0063","doi-asserted-by":"crossref","first-page":"e1003630","DOI":"10.1371\/journal.ppat.1003630","article-title":"HTLV-1 bzip factor induces inflammation through labile FOXP3 expression","volume":"9","author":"Yamamoto-Taguchi","year":"2013","journal-title":"PLoS Pathog"},{"key":"2024061111491812400_CIT0064","doi-asserted-by":"crossref","first-page":"e150472","DOI":"10.1172\/JCI150472","article-title":"HTLV-1 infection promotes excessive T cell activation and transformation into adult T cell leukemia\/lymphoma","volume":"131","author":"Tan","year":"2021","journal-title":"J Clin Invest"},{"key":"2024061111491812400_CIT0065","doi-asserted-by":"crossref","first-page":"1028","DOI":"10.1186\/1471-2164-15-1028","article-title":"Visualisation of the T cell differentiation programme by canonical correspondence analysis of transcriptomes","volume":"15","author":"Ono","year":"2014","journal-title":"BMC Genomics"},{"key":"2024061111491812400_CIT0066","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng.3415","article-title":"Integrated molecular analysis of adult T cell leukemia\/lymphoma","volume":"47","author":"Kataoka","year":"2015","journal-title":"Nat Genet"},{"key":"2024061111491812400_CIT0067","doi-asserted-by":"crossref","first-page":"4821","DOI":"10.1038\/s41467-021-25101-9","article-title":"Chronological genome and single-cell transcriptome integration characterizes the evolutionary process of adult T cell leukemia-lymphoma","volume":"12","author":"Yamagishi","year":"2021","journal-title":"Nat Commun"},{"key":"2024061111491812400_CIT0068","doi-asserted-by":"crossref","first-page":"87","DOI":"10.12688\/wellcomeopenres.12469.2","article-title":"Single-cell heterogeneity and cell-cycle-related viral gene bursts in the human leukaemia virus HTLV-1","volume":"2","author":"Billman","year":"2017","journal-title":"Wellcome Open Res"},{"key":"2024061111491812400_CIT0069","doi-asserted-by":"crossref","first-page":"E1269","DOI":"10.1073\/pnas.1715724115","article-title":"Sporadic on\/off switching of HTLV-1 tax expression is crucial to maintain the whole population of virus-induced leukemic cells","volume":"115","author":"Mahgoub","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2024061111491812400_CIT0070","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1056\/NEJM198308043090501","article-title":"Clinical course of retrovirus-associated adult T-cell lymphoma in the United States","volume":"309","author":"Bunn","year":"1983","journal-title":"N Engl J Med"},{"key":"2024061111491812400_CIT0071","doi-asserted-by":"crossref","first-page":"156","DOI":"10.3960\/jslrt.18032","article-title":"Clinical features and treatment outcomes of opportunistic infections among human T-lymphotrophic virus type 1 (HTLV-1) carriers and patients with adult T-cell leukemia-lymphoma (ATL) at a single institution from 2006 to 2016","volume":"59","author":"Kawano","year":"2019","journal-title":"J Clin Exp Hematop"},{"key":"2024061111491812400_CIT0072","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1365-2249.2004.02524.x","article-title":"Interference with immune function by HTLV-1","volume":"137","author":"Goon","year":"2004","journal-title":"Clin Exp Immunol"},{"key":"2024061111491812400_CIT0073","first-page":"639","article-title":"Immune suppression in healthy carriers of adult T-cell leukemia retrovirus (HTLV-I): Impairment of T-cell control of epstein-barr virus-infected B-cells","volume":"78","author":"Katsuki","year":"1987","journal-title":"Jpn J Cancer Res"},{"key":"2024061111491812400_CIT0074","doi-asserted-by":"crossref","first-page":"3177","DOI":"10.1182\/blood.V97.10.3177","article-title":"Impaired production of naive T lymphocytes in human T-cell leukemia virus type I-infected individuals: its implications in the immunodeficient state","volume":"97","author":"Yasunaga","year":"2001","journal-title":"Blood"},{"key":"2024061111491812400_CIT0075","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1182\/blood-2011-05-357459","article-title":"HTLV-1 bzip factor impairs cell-mediated immunity by suppressing production of th1 cytokines","volume":"119","author":"Sugata","year":"2012","journal-title":"Blood"},{"key":"2024061111491812400_CIT0076","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1126\/science.1155209","article-title":"Coordination of early protective immunity to viral infection by regulatory T cells","volume":"320","author":"Lund","year":"2008","journal-title":"Science"},{"key":"2024061111491812400_CIT0077","doi-asserted-by":"crossref","first-page":"43620","DOI":"10.1074\/jbc.M307275200","article-title":"The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors junb and c-jun and modulates their transcriptional activity","volume":"278","author":"Basbous","year":"2003","journal-title":"J Biol Chem"},{"key":"2024061111491812400_CIT0078","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1182\/blood-2008-06-161729","article-title":"Human T-cell leukemia virus type 1 bzip factor selectively suppresses the classical pathway of nf-kappab","volume":"113","author":"Zhao","year":"2009","journal-title":"Blood"},{"key":"2024061111491812400_CIT0079","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1002\/eji.200738104","article-title":"Human regulatory T cells and autoimmunity","volume":"38","author":"Costantino","year":"2008","journal-title":"Eur J Immunol"},{"key":"2024061111491812400_CIT0080","doi-asserted-by":"crossref","first-page":"7788","DOI":"10.1158\/0008-5472.CAN-10-1736","article-title":"Selective depletion of FOXP3+ regulatory T cells improves effective therapeutic vaccination against established melanoma","volume":"70","author":"Klages","year":"2010","journal-title":"Cancer Res"},{"key":"2024061111491812400_CIT0081","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1200\/JCO.2008.18.7229","article-title":"Tumor-infiltrating FOXP3+ t regulatory cells show strong prognostic significance in colorectal cancer","volume":"27","author":"Salama","year":"2009","journal-title":"J Clin Oncol"},{"key":"2024061111491812400_CIT0082","doi-asserted-by":"crossref","first-page":"75361","DOI":"10.18632\/oncotarget.17722","article-title":"Tumor-infiltrating FOXP3(+) Tregs predict favorable outcome in colorectal cancer patients: a meta-analysis","volume":"8","author":"Hu","year":"2017","journal-title":"Oncotarget"},{"key":"2024061111491812400_CIT0083","doi-asserted-by":"crossref","first-page":"15179","DOI":"10.1038\/srep15179","article-title":"Prognostic value of tumor-infiltrating FOXP3+ regulatory T cells in cancers: a systematic review and meta-analysis","volume":"5","author":"Shang","year":"2015","journal-title":"Sci Rep"},{"key":"2024061111491812400_CIT0084","doi-asserted-by":"crossref","first-page":"E10672","DOI":"10.1073\/pnas.1810580115","article-title":"Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types","volume":"115","author":"Magnuson","year":"2018","journal-title":"Proc Natl Acad Sci USA"},{"key":"2024061111491812400_CIT0085","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.immuni.2019.06.025","article-title":"Inflammation and cancer: triggers, mechanisms, and consequences","volume":"51","author":"Greten","year":"2019","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0086","doi-asserted-by":"crossref","first-page":"10582","DOI":"10.1038\/ncomms10582","article-title":"Melanoma-specific MHC-II expression represents a tumour-autonomous phenotype and predicts response to anti-PD-1\/PD-l1 therapy","volume":"7","author":"Johnson","year":"2016","journal-title":"Nat Commun"},{"key":"2024061111491812400_CIT0087","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1158\/2326-6066.CIR-15-0243","article-title":"Expression of the MHC class II pathway in triple-negative breast cancer tumor cells is associated with a good prognosis and infiltrating lymphocytes","volume":"4","author":"Forero","year":"2016","journal-title":"Cancer Immunol Res"},{"key":"2024061111491812400_CIT0088","doi-asserted-by":"crossref","first-page":"2392","DOI":"10.1158\/1078-0432.CCR-18-3200","article-title":"Biological consequences of MHC-II expression by tumor cells in cancer","volume":"25","author":"Axelrod","year":"2019","journal-title":"Clin Cancer Res"},{"key":"2024061111491812400_CIT0089","doi-asserted-by":"crossref","first-page":"652","DOI":"10.1038\/s41586-021-03326-4","article-title":"CTLA-4 blockade drives loss of Treg stability in glycolysis-low tumours","volume":"591","author":"Zappasodi","year":"2021","journal-title":"Nature"},{"key":"2024061111491812400_CIT0090","doi-asserted-by":"crossref","first-page":"e104","DOI":"10.1200\/JCO.2013.51.3572","article-title":"Combination anti- CTLA-4 and anti-RANKL in metastatic melanoma","volume":"34","author":"Smyth","year":"2014","journal-title":"J Clin Oncol"},{"key":"2024061111491812400_CIT0091","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1158\/2326-6066.CIR-13-0013","article-title":"Anti-CTLA-4 antibodies of IGG2aa isotype enhance antitumor activity through reduction of intratumoral regulatory T cells","volume":"1","author":"Selby","year":"2013","journal-title":"Cancer Immunol Res"},{"key":"2024061111491812400_CIT0092","doi-asserted-by":"crossref","first-page":"1175","DOI":"10.1182\/blood-2007-11-125435","article-title":"CTLA4 blockade expands FOXP3+ regulatory and activated effector CD4+ T cells in a dose-dependent fashion","volume":"112","author":"Kavanagh","year":"2008","journal-title":"Blood"},{"key":"2024061111491812400_CIT0093","doi-asserted-by":"crossref","first-page":"3998","DOI":"10.1016\/j.cell.2021.05.027","article-title":"Expansion of tumor-associated Treg cells upon disruption of a CTLA-4-dependent feedback loop","volume":"184","author":"Marangoni","year":"2021","journal-title":"Cell"},{"key":"2024061111491812400_CIT0094","doi-asserted-by":"crossref","first-page":"1118","DOI":"10.4049\/jimmunol.1200972","article-title":"Cutting edge: cell-extrinsic immune regulation by CTLA-4 expressed on conventional T cells","volume":"189","author":"Wang","year":"2012","journal-title":"J Immunol"},{"key":"2024061111491812400_CIT0095","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1111\/j.1365-2133.2010.10199.x","article-title":"Perturbations of both nonregulatory and regulatory FOXP3+ T cells in patients with malignant melanoma","volume":"164","author":"Fujii","year":"2011","journal-title":"Br J Dermatol"},{"key":"2024061111491812400_CIT0096","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.immuni.2009.03.019","article-title":"Functional delineation and differentiation dynamics of human CD4+ T cells expressing the FOXP3 transcription factor","volume":"30","author":"Miyara","year":"2009","journal-title":"Immunity"},{"key":"2024061111491812400_CIT0097","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1097\/00002281-200307000-00010","article-title":"Immune dysregulation, polyendocrinopathy, enteropathy, and x-linked inheritance (ipex), a syndrome of systemic autoimmunity caused by mutations of FOXP3, a critical regulator of T-cell homeostasis","volume":"15","author":"Gambineri","year":"2003","journal-title":"Curr Opin Rheumatol"},{"key":"2024061111491812400_CIT0098","doi-asserted-by":"crossref","first-page":"a029041","DOI":"10.1101\/cshperspect.a029041","article-title":"Regulatory T cells: from discovery to autoimmunity","volume":"8","author":"Kitz","year":"2018","journal-title":"Cold Spring Harb Perspect Med"},{"key":"2024061111491812400_CIT0099","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1016\/j.jaci.2022.08.003","article-title":"New insights in systemic lupus erythematosus: from regulatory T cells to CAR-T-cell strategies","volume":"150","author":"Doglio","year":"2022","journal-title":"J Allergy Clin Immunol"},{"key":"2024061111491812400_CIT0100","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1007\/978-1-0716-2647-4_12","article-title":"In vitro analysis of CTLA-4-mediated transendocytosis by regulatory T cells","volume":"2559","author":"Waters","year":"2023","journal-title":"Methods Mol Biol"},{"key":"2024061111491812400_CIT0101","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1007\/978-1-0716-2647-4_11","article-title":"Phenotypic and functional studies of human Treg cell subpopulations","volume-title":"Regulatory T-cells: Methods and Protocols","author":"Atif","year":"2023"},{"key":"2024061111491812400_CIT0102","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1007\/978-1-0716-2647-4_1","article-title":"Analysis of the in vivo function of follicular regulatory T (TFR) cells in the regulation of antibody response","volume-title":"Regulatory T-cells: Methods and Protocols","author":"Luo","year":"2023"},{"key":"2024061111491812400_CIT0103","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/978-1-0716-2647-4_2","article-title":"Adoptive transfer and bone marrow chimera models to analyze Treg function and differentiation","volume-title":"Regulatory T-cells: Methods and Protocols","author":"da Silva Domingues","year":"2023"},{"key":"2024061111491812400_CIT0104","doi-asserted-by":"crossref","first-page":"1353","DOI":"10.1038\/ni1536","article-title":"Cd4+CD25+FOXP3+ regulatory T cells induce cytokine deprivation-mediated apoptosis of effector CD4+ T cells","volume":"8","author":"Pandiyan","year":"2007","journal-title":"Nat Immunol"},{"key":"2024061111491812400_CIT0105","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1053\/j.gastro.2024.01.007","article-title":"The FOXP3(+) pro-inflammatory T cell: a potential therapeutic target in Crohn\u2019s disease","volume":"166","author":"Kosinsky","year":"2024","journal-title":"Gastroenterology"}],"container-title":["Discovery Immunology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/discovimmunology\/advance-article-pdf\/doi\/10.1093\/discim\/kyae006\/57567915\/kyae006.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article-pdf\/3\/1\/kyae006\/58196188\/kyae006.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article-pdf\/3\/1\/kyae006\/58196188\/kyae006.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,11]],"date-time":"2024-06-11T21:42:12Z","timestamp":1718142132000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/discovimmunology\/article\/doi\/10.1093\/discim\/kyae006\/7670780"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,1]]},"references-count":105,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2024,1,1]]}},"URL":"https:\/\/doi.org\/10.1093\/discim\/kyae006","relation":{},"ISSN":["2754-2483"],"issn-type":[{"value":"2754-2483","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2024,1,1]]},"published":{"date-parts":[[2024,1,1]]},"article-number":"kyae006"}}