{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:56:44Z","timestamp":1790711804500,"version":"4.1.0"},"reference-count":50,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,6]],"date-time":"2025-04-06T00:00:00Z","timestamp":1743897600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Novartis Deutschland GmbH","award":["MOMB157A_FVSP00"],"award-info":[{"award-number":["MOMB157A_FVSP00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Introduction: The efficacy of anti-CD20 antibodies has significantly contributed to advancing our understanding of disease pathogenesis and improved treatment outcomes in relapsing-remitting multiple sclerosis (RRMS). A comprehensive analysis of the peripheral immune cell profile, combined with prospective clinical characterization, of RRMS patients treated with ocrelizumab (OCR) or ofatumumab (OFA) was performed to further understand immune reconstitution following B-cell depletion. Methods: REBELLION-MS is a longitudinal analysis of RRMS patients treated with either OCR (n = 34) or OFA (n = 25). Analysis of B, T, natural killer (NK) and natural killer T (NKT) cells at baseline, month 1, and 12 was performed by multidimensional flow cytometry. Data were analyzed by conventional gating and unsupervised computational approaches. In parallel, different clinical parameters were longitudinally assessed. Twenty treatment-na\u00efve age\/sex-matched RRMS patients were included as the control cohort. Results: B-cell depletion by OCR and OFA resulted in significant reductions in CD20+ T and B cells as well as B-cell subsets, alongside an expansion of CD5+CD19+CD20\u2212 B cells, while also elevating exhaustion markers (CTLA-4, PD-1, TIGIT, TIM-3) across T, B, NK, and NKT cells. Additionally, regulatory T-cell (TREG) numbers increased, especially in OCR-treated patients, and reductions in double-negative (CD3+CD4\u2212CD8\u2212) T cells (DN T cells) were observed, with these DN T cells having higher CD20 expression compared to CD4 or CD8 positive T cells. These immune profile changes correlated with clinical parameters, suggesting pathophysiological relevance in RRMS. Conclusions: Our interim data add weight to the argumentation that the exhaustion\/activation markers, notably TIGIT, may be relevant to the pathogenesis of MS. In addition, we identify a potentially interesting increase in the expression of CD5+ on B cells. Finally, we identified a population of double-negative T cells (KLRG1+HLADR+, in particular) that is associated with MS activity and decreased with CD20 depletion.<\/jats:p>","DOI":"10.3390\/cells14070552","type":"journal-article","created":{"date-parts":[[2025,4,9]],"date-time":"2025-04-09T12:05:56Z","timestamp":1744200356000},"page":"552","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Effects of Anti-CD20 Antibody Therapy on Immune Cell Dynamics in Relapsing-Remitting Multiple Sclerosis"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0719-8334","authenticated-orcid":false,"given":"Alice G.","family":"Willison","sequence":"first","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramona","family":"Hagler","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Margit","family":"Weise","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4214-4550","authenticated-orcid":false,"given":"Saskia","family":"Elben","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0015-8484","authenticated-orcid":false,"given":"Niklas","family":"Huntemann","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2496-1415","authenticated-orcid":false,"given":"Lars","family":"Masanneck","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steffen","family":"Pfeuffer","sequence":"additional","affiliation":[{"name":"Department of Neurology, University Hospital Giessen and Marburg, Justus-Liebig-University Giessen, 35392 Giessen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4703-2571","authenticated-orcid":false,"given":"Stefanie","family":"Lichtenberg","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"},{"name":"Core Facility Flow Cytometry, Medical Faculty, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristin S.","family":"Golombeck","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lara-Maria","family":"Preuth","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leoni","family":"Rolfes","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Menekse","family":"\u00d6zt\u00fcrk","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6332-8650","authenticated-orcid":false,"given":"Tobias","family":"Ruck","sequence":"additional","affiliation":[{"name":"Department of Neurology with Heimer Institute for Muscle Research, University Hospital Bergmannsheil, 44789 Bochum, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2420-701X","authenticated-orcid":false,"given":"Nico","family":"Melzer","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melanie","family":"Korsen","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen L.","family":"Hauser","sequence":"additional","affiliation":[{"name":"UCSF Weill Institute for Neurosciences, Department of Neurology, University of California, San Francisco, CA 94107, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0614-6989","authenticated-orcid":false,"given":"Hans-Peter","family":"Hartung","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical University of Vienna, 1090 Vienna, Austria"},{"name":"Brain and Mind Center, University of Sydney, Sydney, NSW 2050, Australia"},{"name":"Department of Neurology, Palacky University, 771 46 Olomouc, Czech Republic"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp A.","family":"Lang","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine II, Medical Faculty, Heinrich Heine University, 40225 D\u00fcsseldorf, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Pawlitzki","sequence":"additional","affiliation":[{"name":"Department of Neurology, Medical Faculty and University Hospital, Heinrich Heine University D\u00fcsseldorf, 40225 D\u00fcsseldorf, 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CD20(+) B-Cell-Depleting Therapies in Multiple Sclerosis","volume":"14","author":"Gelfand","year":"2017","journal-title":"Neurotherapeutics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"546","DOI":"10.1056\/NEJMoa1917246","article-title":"Ofatumumab versus Teriflunomide in Multiple Sclerosis","volume":"383","author":"Hauser","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1056\/NEJMoa1601277","article-title":"Ocrelizumab versus Interferon Beta-1a in Relapsing Multiple Sclerosis","volume":"376","author":"Hauser","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1602","DOI":"10.1007\/s13311-021-01048-z","article-title":"A Milestone in Multiple Sclerosis Therapy: Monoclonal Antibodies Against CD20\u2014Yet Progress Continues","volume":"18","author":"Frisch","year":"2021","journal-title":"Neurotherapeutics"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1016\/S1474-4422(17)30470-2","article-title":"Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria","volume":"17","author":"Thompson","year":"2018","journal-title":"Lancet Neurol."},{"key":"ref_6","unstructured":"Willison, A. (2025, March 27). Available online: https:\/\/app.biorender.com\/citation\/6710dafd1080fddf8320d27d."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"978","DOI":"10.1136\/jnnp-2021-328197","article-title":"Immune response to SARS-CoV-2 vaccination in relation to peripheral immune cell profiles among patients with multiple sclerosis receiving ocrelizumab","volume":"93","author":"Korsen","year":"2022","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_8","unstructured":"(2025, March 27). Available online: www.omiq.ai."},{"key":"ref_9","unstructured":"(2025, March 27). Harrington, B. et al., 2004\u20132005. Inkscape, a Vector Graphics Software, to Create the Figures. Available online: http:\/\/www.inkscape.org\/."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"578008","DOI":"10.1016\/j.jneuroim.2022.578008","article-title":"Ocrevus reduces TH40 cells, a biomarker of systemic inflammation, in relapsing multiple sclerosis (RMS) and in progressive multiple sclerosis (PMS)","volume":"374","author":"Curran","year":"2022","journal-title":"J. Neuroimmunol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.2174\/1570159X21666230803161825","article-title":"Ofatumumab and Early Immunological Cells Subset Characterization in Na\u00efve Relapsing Multiple Sclerosis Patients: A Real-World Study","volume":"21","author":"Fantozzi","year":"2023","journal-title":"Curr. Neuropharmacol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e200091","DOI":"10.1212\/NXI.0000000000200091","article-title":"Immune Profiling Reveals the T-Cell Effect of Ocrelizumab in Early Relapsing-Remitting Multiple Sclerosis","volume":"10","author":"Garcia","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e200084","DOI":"10.1212\/NXI.0000000000200084","article-title":"Ocrelizumab Impairs the Phenotype and Function of Memory CD8(+) T Cells: A 1-Year Longitudinal Study in Patients with Multiple Sclerosis","volume":"10","author":"Mathias","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e2207291120","DOI":"10.1073\/pnas.2207291120","article-title":"Differential effects of anti-CD20 therapy on CD4 and CD8 T cells and implication of CD20-expressing CD8 T cells in MS disease activity","volume":"120","author":"Shinoda","year":"2023","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"349","DOI":"10.1016\/j.autrev.2008.11.007","article-title":"CD5: A safeguard against autoimmunity and a shield for cancer cells","volume":"8","author":"Dalloul","year":"2009","journal-title":"Autoimmun. Rev."},{"key":"ref_16","first-page":"79","article-title":"Hiding in plain sight: Time to unlock autoimmune clues in human CD5+ B cells by using nextgen technology","volume":"26","author":"Ahmed","year":"2018","journal-title":"Discov. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1111\/j.1365-3083.1989.tb01104.x","article-title":"Immunohistological analysis of human fetal lymph nodes","volume":"29","author":"Westerga","year":"1989","journal-title":"Scand. J. Immunol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"505","DOI":"10.4049\/jimmunol.136.2.505","article-title":"Leu-1+ (CD5+) B cells. A major lymphoid subpopulation in human fetal spleen: Phenotypic and functional studies","volume":"136","author":"Antin","year":"1986","journal-title":"J. Immunol."},{"key":"ref_19","first-page":"175","article-title":"Coordinate expansion of \u2019fetal type\u2019 lymphocytes (TCR gamma delta+T and CD5+B) in rheumatoid arthritis and primary Sjogren\u2019s syndrome","volume":"77","author":"Brennan","year":"1989","journal-title":"Clin. Exp. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1016\/j.immuni.2008.03.017","article-title":"A regulatory B cell subset with a unique CD1dhiCD5+ phenotype controls T cell-dependent inflammatory responses","volume":"28","author":"Yanaba","year":"2008","journal-title":"Immunity"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.neulet.2009.08.010","article-title":"Memory and naive B-cell subsets in patients with multiple sclerosis","volume":"464","author":"Niino","year":"2009","journal-title":"Neurosci. Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.neulet.2012.06.041","article-title":"CD5-positive B cell subsets in secondary progressive multiple sclerosis","volume":"523","author":"Niino","year":"2012","journal-title":"Neurosci. Lett."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1016\/S0165-5728(02)00360-0","article-title":"Expression of CD5 on B lymphocytes correlates with disease activity in patients with multiple sclerosis","volume":"133","author":"Seidi","year":"2002","journal-title":"J. Neuroimmunol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1172\/JCI22833","article-title":"Intrathecal synthesis of oligoclonal IgM against myelin lipids predicts an aggressive disease course in MS","volume":"115","author":"Villar","year":"2005","journal-title":"J. Clin. Investig."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/0165-5728(91)90004-Q","article-title":"CD5+ B cells and CD4-8-T cells in neuroimmunological diseases","volume":"32","author":"Correale","year":"1991","journal-title":"J. Neuroimmunol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"4801","DOI":"10.4049\/jimmunol.0902385","article-title":"Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity","volume":"184","author":"Watanabe","year":"2010","journal-title":"J. Immunol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1007\/978-1-4899-0274-0_22","article-title":"Regulation of T cell activation by CD28 and CTLA4","volume":"406","author":"Noel","year":"1996","journal-title":"Adv. Exp. Med. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"386","DOI":"10.1038\/nature13848","article-title":"CEACAM1 regulates TIM-3-mediated tolerance and exhaustion","volume":"517","author":"Huang","year":"2015","journal-title":"Nature"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2172","DOI":"10.1016\/j.bbmt.2016.08.007","article-title":"Programmed Death 1 Expression on CD4 + T Cells Predicts Mortality after Allogeneic Stem Cell Transplantation","volume":"22","author":"Schade","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1038\/s43018-023-00690-0","article-title":"PD-1 defines a distinct, functional, tissue-adapted state in Vdelta1(+) T cells with implications for cancer immunotherapy","volume":"5","author":"Davies","year":"2024","journal-title":"Nat. Cancer"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Canaday, D.H., Parker, K.E., Aung, H., Chen, H.E., Nunez-Medina, D., and Burant, C.J. (2013). Age-dependent changes in the expression of regulatory cell surface ligands in activated human T-cells. BMC Immunol., 14.","DOI":"10.1186\/1471-2172-14-45"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jneuroim.2018.08.004","article-title":"CTLA-4, PD-1 and TIM-3 expression predominantly downregulated in MS patients","volume":"323","author":"Mohammadzadeh","year":"2018","journal-title":"J. Neuroimmunol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e156254","DOI":"10.1172\/JCI156254","article-title":"Impaired TIGIT expression on B cells drives circulating follicular helper T cell expansion in multiple sclerosis","volume":"132","author":"Asashima","year":"2022","journal-title":"J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"4984","DOI":"10.4049\/jimmunol.0901038","article-title":"Costimulatory pathways in multiple sclerosis: Distinctive expression of PD-1 and PD-L1 in patients with different patterns of disease","volume":"183","author":"Trabattoni","year":"2009","journal-title":"J. Immunol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4409","DOI":"10.4049\/jimmunol.180.7.4409","article-title":"Lack of TIM-3 immunoregulation in multiple sclerosis","volume":"180","author":"Yang","year":"2008","journal-title":"J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1084\/jem.20060210","article-title":"Dysregulated T cell expression of TIM3 in multiple sclerosis","volume":"203","author":"Koguchi","year":"2006","journal-title":"J. Exp. Med."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"7169","DOI":"10.4049\/jimmunol.172.11.7169","article-title":"T Cell Ig- and mucin-domain-containing molecule-3 (TIM-3) and TIM-1 molecules are differentially expressed on human Th1 and Th2 cells and in cerebrospinal fluid-derived mononuclear cells in multiple sclerosis","volume":"172","author":"Khademi","year":"2004","journal-title":"J. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1007\/s12094-019-02060-8","article-title":"Multiple sclerosis outcomes after cancer immunotherapy","volume":"21","author":"Garcia","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1002\/ana.24715","article-title":"CTLA4 as Immunological Checkpoint in the Development of Multiple Sclerosis","volume":"80","author":"Gerdes","year":"2016","journal-title":"Ann. Neurol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"686","DOI":"10.1177\/1352458516662727","article-title":"ACCLAIM: A randomized trial of abatacept (CTLA4-Ig) for relapsing-remitting multiple sclerosis","volume":"23","author":"Khoury","year":"2017","journal-title":"Mult. Scler. J."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1111","DOI":"10.4049\/jimmunol.1600089","article-title":"Features of Human CD3+CD20+ T Cells","volume":"197","author":"Schuh","year":"2016","journal-title":"J. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"e200140","DOI":"10.1212\/NXI.0000000000200140","article-title":"Intrathecal CD8(+)CD20(+) T Cells in Primary Progressive Multiple Sclerosis","volume":"10","author":"Talbot","year":"2023","journal-title":"Neurol. Neuroimmunol. Neuroinflamm."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1093\/brain\/awy301","article-title":"Proinflammatory CD20+ T cells in the pathogenesis of multiple sclerosis","volume":"142","author":"Hansen","year":"2019","journal-title":"Brain"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1177\/13524585211003301","article-title":"Anti-CD20 therapy corrects a CD8 regulatory T cell deficit in multiple sclerosis","volume":"27","author":"Feng","year":"2021","journal-title":"Mult. Scler."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.jneuroim.2019.04.017","article-title":"B cell depletion with ublituximab reshapes the T cell profile in multiple sclerosis patients","volume":"332","author":"Gormley","year":"2019","journal-title":"J. Neuroimmunol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1111\/imm.13441","article-title":"Double-negative T cells: Setting the stage for disease control or progression","volume":"165","author":"Velikkakam","year":"2021","journal-title":"Immunology"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Wu, Z., Zheng, Y., Sheng, J., Han, Y., Yang, Y., Pan, H., and Yao, J. (2022). CD3(+)CD4(-)CD8(-) (Double-Negative) T Cells in Inflammation, Immune Disorders and Cancer. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.816005"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"8761","DOI":"10.4049\/jimmunol.181.12.8761","article-title":"Expanded double negative T cells in patients with systemic lupus erythematosus produce IL-17 and infiltrate the kidneys","volume":"181","author":"Oukka","year":"2008","journal-title":"J. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"103","DOI":"10.4049\/jimmunol.143.1.103","article-title":"T cell receptor alpha\/beta expressing double-negative (CD4-\/CD8-) and CD4+ T helper cells in humans augment the production of pathogenic anti-DNA autoantibodies associated with lupus nephritis","volume":"143","author":"Shivakumar","year":"1989","journal-title":"J. Immunol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5338","DOI":"10.4049\/jimmunol.165.9.5338","article-title":"Human Double-Negative T Cells in Systemic Lupus Erythematosus Provide Help for IgG and Are Restricted by CD1c","volume":"165","author":"Sieling","year":"2000","journal-title":"J. Immunol."}],"container-title":["Cells"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/7\/552\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:11:13Z","timestamp":1760029873000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4409\/14\/7\/552"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,6]]},"references-count":50,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2025,4]]}},"alternative-id":["cells14070552"],"URL":"https:\/\/doi.org\/10.3390\/cells14070552","relation":{},"ISSN":["2073-4409"],"issn-type":[{"value":"2073-4409","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,6]]}}}