{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T11:02:10Z","timestamp":1784718130410,"version":"3.55.0"},"reference-count":47,"publisher":"Portland Press Ltd.","issue":"8","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["N\/A"],"award-info":[{"award-number":["N\/A"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["portlandpress.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bystander activation represents an innate-like mechanism by which T cells, particularly effector and memory subsets, can become activated in the absence of cognate antigen recognition. Using human tonsil organoid cultures as a physiologically relevant model, we investigated the bystander activation of CD4+ memory T cells in situ in comparison with superantigen stimulation. Tonsillar T cells were stimulated with pertussis toxin\u2014a component of the childhood pertussis vaccine\u2014in comparison with toxic shock syndrome toxin-1 (TSST-1) as the staphylococcal superantigen and assessed for activation status, cytokine expression, RNA expression, and metabolic reprogramming. We observed robust T cell activation and cytokine production as well as transcriptional changes comparable to those elicited by TSST-1. Notably, both bystander- and superantigen-activated T memory cells exhibited a metabolic shift toward glycolysis as the dominant energy pathway. These findings demonstrate the similarities between bystander and superantigen-induced T cell activation and show up pathways to sway bystander activation depending on the immunological context.<\/jats:p>","DOI":"10.1042\/cs20261341","type":"journal-article","created":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T09:24:44Z","timestamp":1783502684000},"page":"1725-1740","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Pertussis toxin as well as\n                    <i>staphylococcal<\/i>\n                    superantigen induce glycolysis as energy source during T cell activation in an adenoid organoid model"],"prefix":"10.1042","volume":"140","author":[{"given":"Christopher\u00a0T.","family":"Neullens","sequence":"first","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"K\u00fchne","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"},{"name":"2Department of Paediatrics, Pediatric Rheumatology, Inselspital, Bern University Hospital, University of Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renske","family":"de\u00a0Jong","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anandhi","family":"Rajendiran","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christoph","family":"Kessel","sequence":"additional","affiliation":[{"name":"3Translational Inflammation Research, Universit\u00e4tsklinikum M\u00fcnster, M\u00fcnster, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabrina\u00a0B.","family":"Bennstein","sequence":"additional","affiliation":[{"name":"4Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justus","family":"Ilgner","sequence":"additional","affiliation":[{"name":"5Department of Otorhinolaryngology, Head and Neck Surgery, RWTH Aachen University Hospital, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Goncalves","sequence":"additional","affiliation":[{"name":"5Department of Otorhinolaryngology, Head and Neck Surgery, RWTH Aachen University Hospital, Aachen, Germany"},{"name":"6Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sebastian\u00a0P.","family":"Schraven","sequence":"additional","affiliation":[{"name":"5Department of Otorhinolaryngology, Head and Neck Surgery, RWTH Aachen University Hospital, Aachen, Germany"},{"name":"7Clinic for Otorhinolaryngology, Head, Neck and Facial Plastic Surgery, and Communication Disorders (Hearing, Voice and Speech Disorders), Fulda Hospital, Fulda, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephan","family":"Hackenberg","sequence":"additional","affiliation":[{"name":"5Department of Otorhinolaryngology, Head and Neck Surgery, RWTH Aachen University Hospital, Aachen, Germany"},{"name":"6Oto-Rhino-Laryngology, Head and Neck Surgery, University Hospital W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dirk","family":"Baumjohann","sequence":"additional","affiliation":[{"name":"8Medical Clinic III for Oncology, Haematology, Immuno-Oncology and Rheumatology, University Hospital Bonn, University of Bonn, Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kim","family":"Ohl","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"},{"name":"4Institute of Immunology, Medical Faculty, RWTH Aachen University, Aachen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3566-227X","authenticated-orcid":false,"given":"Klaus","family":"Tenbrock","sequence":"additional","affiliation":[{"name":"1Department of Pediatrics, Paediatric Rheumatology, Medical Faculty, RWTH Aachen University, Aachen, Germany"},{"name":"2Department of Paediatrics, Pediatric Rheumatology, Inselspital, Bern University Hospital, University of Bern, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"2026072206163861300_B1","doi-asserted-by":"publisher","first-page":"1127470","DOI":"10.3389\/fimmu.2023.1127470","article-title":"Antigen-specificity measurements are the key to understanding T cell responses","volume":"14","author":"Tippalagama","year":"2023","journal-title":"Front. Immunol."},{"key":"2026072206163861300_B2","doi-asserted-by":"publisher","first-page":"1021","DOI":"10.1016\/j.it.2018.10.003","article-title":"Bystander T cells: a balancing act of friends and foes","volume":"39","author":"Whiteside","year":"2018","journal-title":"Trends Immunol."},{"key":"2026072206163861300_B3","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1038\/s12276-020-00486-7","article-title":"Bystander CD4+ T cells: crossroads between innate and adaptive immunity","volume":"52","author":"Lee","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"2026072206163861300_B4","doi-asserted-by":"publisher","first-page":"1465889","DOI":"10.3389\/fimmu.2024.1465889","article-title":"Mechanisms governing bystander activation of T cells","volume":"15","author":"Yosri","year":"2024","journal-title":"Front. Immunol."},{"key":"2026072206163861300_B5","doi-asserted-by":"publisher","first-page":"417","DOI":"10.1038\/s41577-023-00979-2","article-title":"Novel insights into the immune response to bacterial T cell superantigens","volume":"24","author":"Tuffs","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"2026072206163861300_B6","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1146\/annurev-immunol-120419-022408","article-title":"Germinal centers","volume":"40","author":"Victora","year":"2022","journal-title":"Annu. Rev. Immunol."},{"key":"2026072206163861300_B7","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1186\/s13073-018-0584-8","article-title":"Advanced model systems and tools for basic and translational human immunology","volume":"10","author":"Wagar","year":"2018","journal-title":"Genome Med."},{"key":"2026072206163861300_B8","doi-asserted-by":"publisher","first-page":"1343","DOI":"10.1016\/j.immuni.2022.07.008","article-title":"Standing on the shoulders of mice","volume":"55","author":"Medetgul-Ernar","year":"2022","journal-title":"Immunity"},{"key":"2026072206163861300_B9","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1016\/j.immuni.2023.06.019","article-title":"Influenza vaccine format mediates distinct cellular and antibody responses in human immune organoids","volume":"56","author":"Kastenschmidt","year":"2023","journal-title":"Immunity"},{"key":"2026072206163861300_B10","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/s41577-023-00956-9","article-title":"Human immune organoids: a tool to study vaccine responses","volume":"23","author":"Wagar","year":"2023","journal-title":"Nat. Rev. Immunol."},{"key":"2026072206163861300_B11","doi-asserted-by":"publisher","first-page":"267","DOI":"10.1007\/978-1-0716-1736-6_22","article-title":"3D tissue explant and single-cell suspension organoid culture systems for ex vivo drug testing on human tonsil-derived T follicular helper cells","volume":"2380","author":"Schmidt","year":"2022","journal-title":"Methods Mol. Biol."},{"key":"2026072206163861300_B12","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/s44321-025-00193-8","article-title":"Boosting human immunology: harnessing the potential of immune organoids","volume":"17","author":"Moll","year":"2025","journal-title":"EMBO Mol. Med."},{"key":"2026072206163861300_B13","doi-asserted-by":"publisher","first-page":"102684","DOI":"10.1016\/j.ebiom.2020.102684","article-title":"Complex human adenoid tissue-based ex vivo culture systems reveal anti-inflammatory drug effects on germinal center T and B cells","volume":"53","author":"Schmidt","year":"2020","journal-title":"eBioMedicine"},{"key":"2026072206163861300_B14","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1038\/s41591-020-01145-0","article-title":"Modeling human adaptive immune responses with tonsil organoids","volume":"27","author":"Wagar","year":"2021","journal-title":"Nat. Med."},{"key":"2026072206163861300_B15","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/j.1600-065X.2012.01150.x","article-title":"Metabolic switching and fuel choice during T-cell differentiation and memory development","volume":"249","author":"van der Windt","year":"2012","journal-title":"Immunol. Rev."},{"key":"2026072206163861300_B16","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1038\/ni.2556","article-title":"Control of amino-acid transport by antigen receptors coordinates the metabolic reprogramming essential for T cell differentiation","volume":"14","author":"Sinclair","year":"2013","journal-title":"Nat. Immunol."},{"key":"2026072206163861300_B17","doi-asserted-by":"publisher","first-page":"e202451066","DOI":"10.1002\/eji.202451066","article-title":"Human genetic GLUT1 deficiency results in impaired T cellular IFN-gamma production","volume":"55","author":"Jong","year":"2025","journal-title":"Eur. J. Immunol."},{"key":"2026072206163861300_B18","doi-asserted-by":"publisher","first-page":"769","DOI":"10.1016\/S1074-7613(02)00323-0","article-title":"The CD28 signaling pathway regulates glucose metabolism","volume":"16","author":"Frauwirth","year":"2002","journal-title":"Immunity"},{"key":"2026072206163861300_B19","doi-asserted-by":"publisher","first-page":"4476","DOI":"10.4049\/jimmunol.180.7.4476","article-title":"Glucose uptake is limiting in T cell activation and requires CD28-mediated Akt-dependent and independent pathways","volume":"180","author":"Jacobs","year":"2008","journal-title":"J. Immunol."},{"key":"2026072206163861300_B20","doi-asserted-by":"publisher","first-page":"750","DOI":"10.1038\/s12276-020-0435-8","article-title":"Recent insights of T cell receptor-mediated signaling pathways for T cell activation and development","volume":"52","author":"Hwang","year":"2020","journal-title":"Exp. Mol. Med."},{"key":"2026072206163861300_B21","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.smim.2016.10.009","article-title":"Metabolic pathways in T cell activation and lineage differentiation","volume":"28","author":"Almeida","year":"2016","journal-title":"Semin. Immunol."},{"key":"2026072206163861300_B22","doi-asserted-by":"publisher","first-page":"497","DOI":"10.1016\/j.molimm.2015.07.027","article-title":"Metabolic regulation of T cell differentiation and function","volume":"68","author":"Park","year":"2015","journal-title":"Mol. Immunol."},{"key":"2026072206163861300_B23","doi-asserted-by":"publisher","first-page":"1063","DOI":"10.1016\/j.cmet.2020.11.007","article-title":"SCENITH: a flow cytometry-based method to functionally profile energy metabolism with single-cell resolution","volume":"32","author":"Arguello","year":"2020","journal-title":"Cell Metab."},{"key":"2026072206163861300_B24","doi-asserted-by":"publisher","first-page":"276","DOI":"10.1038\/s41587-020-0439-x","article-title":"The nf-core framework for community-curated bioinformatics pipelines","volume":"38","author":"Ewels","year":"2020","journal-title":"Nat. Biotechnol."},{"key":"2026072206163861300_B25","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1038\/nbt.3820","article-title":"Nextflow enables reproducible computational workflows","volume":"35","author":"Di Tommaso","year":"2017","journal-title":"Nat. Biotechnol."},{"key":"2026072206163861300_B26","article-title":"FelixKrueger\/TrimGalore: v0.6.7","volume-title":"Zenodo","author":"Krueger","year":"2021"},{"key":"2026072206163861300_B27","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"2026072206163861300_B28","doi-asserted-by":"publisher","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"2026072206163861300_B29","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"Yu","year":"2012","journal-title":"OMICS"},{"key":"2026072206163861300_B30","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41467-017-02391-6","article-title":"Perturbation-response genes reveal signaling footprints in cancer gene expression","volume":"9","author":"Schubert","year":"2018","journal-title":"Nat. Commun."},{"key":"2026072206163861300_B31","doi-asserted-by":"publisher","first-page":"vbac016","DOI":"10.1093\/bioadv\/vbac016","article-title":"decoupleR: ensemble of computational methods to infer biological activities from omics data","volume":"2","author":"Badia","year":"2022","journal-title":"Bioinform. Adv."},{"key":"2026072206163861300_B32","doi-asserted-by":"publisher","DOI":"10.1136\/bmjpo-2022-001710","article-title":"Adenoid hypertrophy in children: a narrative review of pathogenesis and clinical relevance","volume":"7","author":"Niedzielski","year":"2023","journal-title":"BMJ Paediatr. Open"},{"key":"2026072206163861300_B33","doi-asserted-by":"publisher","first-page":"2272","DOI":"10.3390\/toxins2092272","article-title":"Staphylococcal superantigen (TSST-1) mutant analysis reveals that t cell activation is required for biological effects in the rabbit including the cytokine storm","volume":"2","author":"Stich","year":"2010","journal-title":"Toxins (Basel)"},{"key":"2026072206163861300_B34","doi-asserted-by":"publisher","first-page":"S305","DOI":"10.1093\/clinids\/11.Supplement_1.S305","article-title":"Stimulation of T cells and induction of interferon by toxic shock syndrome toxin 1","volume":"11","author":"Micusan","year":"1989","journal-title":"Rev. Infect. Dis."},{"key":"2026072206163861300_B35","doi-asserted-by":"publisher","first-page":"2195","DOI":"10.1101\/gad.1228704","article-title":"Signaling to NF-kappaB","volume":"18","author":"Hayden","year":"2004","journal-title":"Genes Dev."},{"key":"2026072206163861300_B36","doi-asserted-by":"publisher","first-page":"2044","DOI":"10.1158\/1078-0432.CCR-12-3603","article-title":"Molecular pathways: interleukin-15 signaling in health and in cancer","volume":"20","author":"Mishra","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"2026072206163861300_B37","doi-asserted-by":"publisher","first-page":"310","DOI":"10.1016\/j.it.2017.01.006","article-title":"IL-17 signaling: the Yin and the Yang","volume":"38","author":"Amatya","year":"2017","journal-title":"Trends Immunol."},{"key":"2026072206163861300_B38","doi-asserted-by":"publisher","first-page":"411","DOI":"10.1146\/annurev-immunol-042617-053352","article-title":"Signaling and function of interleukin-2 in T lymphocytes","volume":"36","author":"Ross","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"2026072206163861300_B39","doi-asserted-by":"publisher","first-page":"107950","DOI":"10.1016\/j.jbc.2024.107950","article-title":"Alpha-1 antitrypsin inhibits pertussis toxin","volume":"300","author":"Lietz","year":"2024","journal-title":"J. Biol. Chem."},{"key":"2026072206163861300_B40","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41392-025-02141-x","article-title":"Energy metabolism in health and diseases","volume":"10","author":"Liu","year":"2025","journal-title":"Signal Transduct. Target. Ther."},{"key":"2026072206163861300_B41","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.immuni.2006.04.012","article-title":"Bacterial superantigens bypass Lck-dependent T cell receptor signaling by activating a Galpha11-dependent, PLC-beta-mediated pathway","volume":"25","author":"Bueno","year":"2006","journal-title":"Immunity"},{"key":"2026072206163861300_B42","doi-asserted-by":"publisher","first-page":"557","DOI":"10.1038\/s41590-025-02105-x","article-title":"The integrated stress response pathway controls cytokine production in tissue-resident memory CD4+ T cells","volume":"26","author":"Asada","year":"2025","journal-title":"Nat. Immunol."},{"key":"2026072206163861300_B43","doi-asserted-by":"publisher","first-page":"102299","DOI":"10.1016\/j.coi.2023.102299","article-title":"Bystander activation in memory and antigen-inexperienced memory-like CD8 T cells","volume":"82","author":"Paprckova","year":"2023","journal-title":"Curr. Opin. Immunol."},{"key":"2026072206163861300_B44","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.1007\/s00103-009-0960-z","article-title":"Childhood vaccination schedules in Europe vary widely. Is this a problem?","volume":"52","author":"Lopalco","year":"2009","journal-title":"Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz"},{"key":"2026072206163861300_B45","doi-asserted-by":"publisher","first-page":"e518","DOI":"10.1093\/infdis\/jiae034","article-title":"IL-17 and IFN-gamma-producing respiratory tissue-resident memory CD4 T cells persist for decades in adults immunized as children with whole-cell pertussis vaccines","volume":"230","author":"McCarthy","year":"2024","journal-title":"J. Infect. Dis."},{"key":"2026072206163861300_B46","doi-asserted-by":"publisher","first-page":"e2250247","DOI":"10.1002\/eji.202250247","article-title":"Bystander activation of Bordetella pertussis-induced nasal tissue-resident memory CD4 T cells confers heterologous immunity to Klebsiella pneumoniae","volume":"53","author":"Curham","year":"2023","journal-title":"Eur. J. Immunol."},{"key":"2026072206163861300_B47","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1093\/nar\/30.1.207","article-title":"Gene Expression Omnibus: NCBI gene expression and hybridization array data repository","volume":"30","author":"Edgar","year":"2002","journal-title":"Nucleic Acids Res."}],"container-title":["Clinical Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/140\/8\/1725\/990052\/cs-2026-1341.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/portlandpress.com\/clinsci\/article-pdf\/140\/8\/1725\/990052\/cs-2026-1341.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T10:16:42Z","timestamp":1784715402000},"score":1,"resource":{"primary":{"URL":"https:\/\/portlandpress.com\/clinsci\/article\/140\/8\/1725\/237809\/Pertussis-toxin-as-well-as-staphylococcal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":47,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,8,12]]}},"URL":"https:\/\/doi.org\/10.1042\/cs20261341","relation":{},"ISSN":["0143-5221","1470-8736"],"issn-type":[{"value":"0143-5221","type":"print"},{"value":"1470-8736","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,8]]},"published":{"date-parts":[[2026,7,22]]}}}