{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T00:10:59Z","timestamp":1792714259415,"version":"4.5.0"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T00:00:00Z","timestamp":1758499200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disease of the central nervous system, primarily characterized by anti-AQP4 antibodies. While, treatment for preventing recurrence of NMOSD predominantly focuses on the production of anti-AQP4 antibodies and the subsequent inflammatory response, one effective strategy is targeting B cells, investigating the status of T lymphocytes during NMOSD onset holds significant importance for elucidating disease mechanisms and identifying potential novel therapeutic approaches.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Peripheral blood samples were collected from NMOSD patients with acute exacerbation. The NMOSD patients were divided into the pre- glucocorticoid treatment NMOSD patient group (PRE) and the glucocorticoid treatment NMOSD patient group (GC) based on whether they received glucocorticoid therapy. Healthy controls were included at the same time. Flow cytometry was employed to analyze differences in T cell compartment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Multivariate linear regression analysis adjusted for age revealed that the GC group had fewer CD8+ TEM cells than controls (\u03b2=-14.96, P=0.002). In addition, the PRE group had higher frequencies of HLA-DR+CD38+ CD4+ cells and HLA-DR+ CD4+ T cells compared to the control group (P= 0.005, P= 0.004, respectively), the frequency of HLA-DR+ CD4+ T cells in PRE group was higher than the GC group (P= 0.007). The multivariate analysis results showed that in CD4+ T cells, the frequency of Th1Th17 cells in the PRE patient group was higher than that in the control group (\u03b2= 6.37, 98.33% CI:1.96-10.78, P = 0.001), and the frequency of Th2 cells in the PRE group was lower than that in the control group (\u03b2=-11.41, 98.33% CI: -22.26\u2013 -0.55, P = 0.012).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These findings underscore the pivotal role of Th1Th17 and Th17 cells in NMOSD pathogenesis. Exploring intervention strategies targeting Th17 cells or T cell activation (e.g., HLA-DR-targeted therapies) may hold clinical relevance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fimmu.2025.1654533","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T05:30:34Z","timestamp":1758519034000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Changes in T lymphocyte subsets in patients with acute neuromyelitis optica spectrum disorder"],"prefix":"10.3389","volume":"16","author":[{"given":"Ying-Zhe","family":"Shao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tao-Feng","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin-Jie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiu-Xia","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000001729","article-title":"International consensus diagnostic criteria for neuromyelitis optica spectrum disorders","volume":"85","author":"Wingerchuk","year":"2015","journal-title":"Neurology"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2021.102921","article-title":"Comparisons of clinical phenotype, radiological and laboratory features, and therapy of neuromyelitis optica spectrum disorder by regions: update and challenges","volume":"21","author":"Liu","year":"2022","journal-title":"Autoimmun Rev"},{"key":"B3","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1212\/WNL.0000000000011153","article-title":"Worldwide incidence and prevalence of neuromyelitis optica: A systematic review","volume":"96","author":"Papp","year":"2021","journal-title":"Neurology"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2020.102542","article-title":"Neuromyelitis optica spectrum disorder in China: Quality of life and medical care experience","volume":"46","author":"Huang","year":"2020","journal-title":"Mult Scler Relat Disord"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2023.103465","article-title":"A comprehensive review of the advances in neuromyelitis optica spectrum disorder","volume":"22","author":"Siriratnam","year":"2023","journal-title":"Autoimmun Rev"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-024-07079-8","article-title":"B cells orchestrate tolerance to the neuromyelitis optica autoantigen AQP4","volume":"627","author":"Afzali","year":"2024","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02247","article-title":"Immunosenescence and its hallmarks: how to oppose aging strategically? A review of potential options for therapeutic intervention","volume":"10","author":"Aiello","year":"2019","journal-title":"Front Immunol"},{"key":"B8","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1002\/acn3.51241","article-title":"CD8+ T cell subpopulations and pro-inflammatory cytokines in neuromyelitis optica spectrum disorder","volume":"8","author":"Shi","year":"2021","journal-title":"Ann Clin Transl Neurol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1016\/j.ebiom.2022.104179","article-title":"Immune aging in multiple sclerosis is characterized by abnormal CD4 T cell activation and increased frequencies of cytotoxic CD4 T cells with advancing age","volume":"82","author":"Zuroff","year":"2022","journal-title":"eBioMedicine"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5314541","article-title":"Th17 cells pathways in multiple sclerosis and neuromyelitis optica spectrum disorders: pathophysiological and therapeutic implications","volume":"2016","author":"Dos Passos","year":"2016","journal-title":"Mediators Inflammation"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2015.00504","article-title":"Memory T cell migration","volume":"6","author":"Zhang","year":"2015","journal-title":"Front Immunol"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-immunol-032712-095954","article-title":"Memory T cell subsets, migration patterns, and tissue residence","volume":"31","author":"Mueller","year":"2013","journal-title":"Annu Rev Immunol"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2004.07.001","article-title":"Age-associated changes in the frequency of na\u00efve, memory and effector CD8+ T cells","volume":"125","author":"Hong","year":"2004","journal-title":"Mech Ageing Dev"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2005.11.001","article-title":"Accumulation of memory T cells from childhood to old age: central and effector memory cells in CD4(+) versus effector memory and terminally differentiated memory cells in CD8(+) compartment","volume":"127","author":"Saule","year":"2006","journal-title":"Mech Ageing Dev"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00170","article-title":"Role of memory T cells in allograft rejection and tolerance","volume":"8","author":"Benichou","year":"2017","journal-title":"Front Immunol"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/imm.13843","article-title":"The role and therapeutic strategies for tissue-resident memory T cells, central memory T cells, and effector memory T cells in psoriasis","volume":"173","author":"Deng","year":"2024","journal-title":"Immunology"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1574455","article-title":"Highly differentiated T cells link systemic and vascular inflammation in a mouse model of recurrent psoriasis","volume":"16","author":"Casciano","year":"2025","journal-title":"Front Immunol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2023.1297577","article-title":"Single-cell immunophenotyping revealed the association of CD4+ central and CD4+ effector memory T cells linking exacerbating chronic obstructive pulmonary disease and NSCLC","volume":"14","author":"G\u00e9mes","year":"2023","journal-title":"Front Immunol"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1172\/JCI123726","article-title":"Dengue-specific CD8+ T cell subsets display specialized transcriptomic and TCR profiles","volume":"129","author":"Tian","year":"2019","journal-title":"J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1177\/1352458514536252","article-title":"Deficiency of CD8+ effector memory T cells is an early and persistent feature of multiple sclerosis","volume":"20","author":"Pender","year":"2014","journal-title":"Mult Scler"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s00415-024-12571-2","article-title":"Cytomegalovirus and Epstein-Barr virus infections in patients with neuromyelitis optica spectrum disorder","volume":"271","author":"Shi","year":"2024","journal-title":"J Neurol"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2024.105923","article-title":"Preceding hepatitis B virus infection is highly prevalent in patients with neuromyelitis optica spectrum disorder in Taiwan","volume":"92","author":"Ou Yang","year":"2024","journal-title":"Mult Scler Relat Disord"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1016\/j.msard.2025.106316","article-title":"Impact of COVID-19 and vaccination on multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD)","volume":"95","author":"Apiwattanakul","year":"2025","journal-title":"Mult Scler Relat Disord"},{"key":"B24","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.thromres.2019.05.010","article-title":"Excessive expressions of T cell activation markers in pediatric immune thrombocytopenia","volume":"180","author":"Chen","year":"2019","journal-title":"Thromb Res"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.48051","article-title":"Multiplexed imaging of immune cells in staged multiple sclerosis lesions by mass cytometry","volume":"8","author":"Ramaglia","year":"2019","journal-title":"Elife"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1136\/jnnp-2023-332224","article-title":"T cell activation markers CD38 and HLA-DR indicative of non-seroconversion in anti-CD20-treated patients with multiple sclerosis following SARS-CoV-2 mRNA vaccination","volume":"95","author":"Verstegen","year":"2024","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B27","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1210\/edrv-17-1-64","article-title":"Immune-neuro-endocrine interactions: facts and hypotheses","volume":"17","author":"Besedovsky","year":"1996","journal-title":"Endocr Rev"},{"key":"B28","doi-asserted-by":"publisher","first-page":"60","DOI":"10.1007\/s00018-005-5390-y","article-title":"Glucocorticoids in T cell apoptosis and function","volume":"63","author":"Herold","year":"2006","journal-title":"Cell Mol Life Sci"},{"key":"B29","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.mce.2010.04.005","article-title":"The anti-inflammatory and immunosuppressive effects of glucocorticoids, recent developments and mechanistic insights","volume":"335","author":"Coutinho","year":"2011","journal-title":"Mol Cell Endocrinol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-05-078154","article-title":"CD4 T cells: fates, functions, and faults","volume":"112","author":"Zhu","year":"2008","journal-title":"Blood"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/nature04790","article-title":"Interleukin-2 signals during priming are required for secondary expansion of CD8+ memory T cells","volume":"441","author":"Williams","year":"2006","journal-title":"Nature"},{"key":"B32","doi-asserted-by":"publisher","first-page":"485","DOI":"10.1146\/annurev.immunol.021908.132710","article-title":"IL-17 and th17 cells","volume":"27","author":"Korn","year":"2009","journal-title":"Annu Rev Immunol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1002\/art.21749","article-title":"Synovial membrane cytokine expression is predictive of joint damage progression in rheumatoid arthritis: a two-year prospective study (the DAMAGE study cohort)","volume":"54","author":"Kirkham","year":"2006","journal-title":"Arthritis Rheum"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awy069","article-title":"T helper 17.1 cells associate with multiple sclerosis disease activity: perspectives for early intervention","volume":"141","author":"van Langelaar","year":"2018","journal-title":"Brain"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2023.11.003","article-title":"T helper (Th) cell profiles and cytokines\/chemokines in characterization, treatment, and monitoring of autoimmune diseases","volume":"220","author":"Ayass","year":"2023","journal-title":"Methods"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.2147\/NDT.S425759","article-title":"Peripheral blood th1\/th17 immune cell shift is associated with disease activity and severity of AQP4 antibody sero-positive neuromyelitis optica spectrum disorder","volume":"19","author":"Cao","year":"2023","journal-title":"Neuropsychiatr Dis Treat"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2377-10-113","article-title":"Expression of chemokine receptors on peripheral blood lymphocytes in multiple sclerosis and neuromyelitis optica","volume":"10","author":"Uzawa","year":"2010","journal-title":"BMC Neurol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awab102","article-title":"Staging of astrocytopathy and complement activation in neuromyelitis optica spectrum disorders","volume":"144","author":"Takai","year":"2021","journal-title":"Brain"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1016\/j.intimp.2019.105793","article-title":"Proportions of Th17 cells and Th17-related cytokines in neuromyelitis optica spectrum disorders patients: A meta-analysis","volume":"75","author":"Hou","year":"2019","journal-title":"Int Immunopharmacol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1038\/ni1254","article-title":"Interleukin 17-producing CD4+ effector T cells develop via a lineage distinct from the T helper type 1 and 2 lineages","volume":"6","author":"Harrington","year":"2005","journal-title":"Nat Immunol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/ni1261","article-title":"A distinct lineage of CD4 T cells regulates tissue inflammation by producing interleukin 17","volume":"6","author":"Park","year":"2005","journal-title":"Nat Immunol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.jns.2013.03.002","article-title":"Role of Th17 cells in the pathogenesis of CNS inflammatory demyelination","volume":"333","author":"Rostami","year":"2013","journal-title":"J Neurol Sci"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2022.845011","article-title":"IL-17A Mediates Demyelination by Activating A1 Astrocytes via SOCS3 During Angiostrongylus cantonensis Infection","volume":"13","author":"Zhou","year":"2022","journal-title":"Front Immunol"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2006","DOI":"10.1016\/j.immuni.2023.06.012","article-title":"An autonomous activation of interleukin-17 receptor signaling sustains inflammation and promotes disease progression","volume":"56","author":"Luo","year":"2023","journal-title":"Immunity"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24097960","article-title":"Autoimmune neuroinflammatory diseases: role of interleukins","volume":"24","author":"Khan","year":"2023","journal-title":"Int J Mol Sci"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbi.2010.01.014","article-title":"Infiltration of Th1 and Th17 cells and activation of microglia in the CNS during the course of experimental autoimmune encephalomyelitis","volume":"24","author":"Murphy","year":"2010","journal-title":"Brain Behav Immun"}],"container-title":["Frontiers in Immunology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1654533\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T05:30:34Z","timestamp":1758519034000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fimmu.2025.1654533\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,9,22]]},"references-count":46,"alternative-id":["10.3389\/fimmu.2025.1654533"],"URL":"https:\/\/doi.org\/10.3389\/fimmu.2025.1654533","relation":{},"ISSN":["1664-3224"],"issn-type":[{"value":"1664-3224","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,9,22]]},"article-number":"1654533"}}