{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T11:07:53Z","timestamp":1784632073344,"version":"3.55.0"},"reference-count":39,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000268","name":"Biotechnology and Biological Sciences Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000268","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000265","name":"Medical Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000265","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clin Experimental Allergy"],"published-print":{"date-parts":[[2024,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Vancomycin, a glycopeptide antibiotic used for Gram\u2010positive bacterial infections, has been linked with drug reaction with eosinophilia and systemic symptoms (DRESS) in HLA\u2010A*32:01\u2010expressing individuals. This is associated with activation of T lymphocytes, for which glycolysis has been isolated as a fuel pathway following antigenic stimulation. However, the metabolic processes that underpin drug\u2010reactive T\u2010cell activation are currently undefined and may shed light on the energetic conditions needed for the elicitation of drug hypersensitivity or tolerogenic pathways. Here, we sought to characterise the immunological and metabolic pathways involved in drug\u2010specific T\u2010cell activation within the context of DRESS pathogenesis using vancomycin as model compound and drug\u2010reactive T\u2010cell clones (TCCs) generated from healthy donors and vancomycin\u2010hypersensitive patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>CD4+ and CD8+ vancomycin\u2010responsive TCCs were generated by serial dilution. The Seahorse XFe<jats:sup>96<\/jats:sup> Analyzer was used to measure the extracellular acidification rate (ECAR) as an indicator of glycolytic function. Additionally, T\u2010cell proliferation and cytokine release (IFN\u2010\u03b3) assay were utilised to correlate the bioenergetic characteristics of T\u2010cell activation with in\u00a0vitro assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Model T\u2010cell stimulants induced non\u2010specific T\u2010cell activation, characterised by immediate augmentation of ECAR and rate of ATP production (JATPglyc). There was a dose\u2010dependent and drug\u2010specific glycolytic shift when vancomycin\u2010reactive TCCs were exposed to the drug. Vancomycin\u2010reactive TCCs did not exhibit T\u2010cell cross\u2010reactivity with structurally similar compounds within proliferative and cytokine readouts. However, cross\u2010reactivity was observed when analysing energetic responses; TCCs with prior specificity for vancomycin were also found to exhibit glycolytic switching after exposure to teicoplanin. Glycolytic activation of TCC was HLA restricted, as exposure to HLA blockade attenuated the glycolytic induction.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>These studies describe the glycolytic shift of CD4+ and CD8+ T cells following vancomycin exposure. Since similar glycolytic switching is observed with teicoplanin, which did not activate T cells, it is possible the master switch for T\u2010cell activation is located upstream of metabolic signalling.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cea.14423","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T03:55:20Z","timestamp":1704426920000},"page":"21-33","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Glycolysis: An early marker for vancomycin\u2010specific T\u2010cell activation"],"prefix":"10.1111","volume":"54","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4520-108X","authenticated-orcid":false,"given":"Joshua","family":"Gardner","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Centre for Drug Safety Science University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean","family":"Hammond","sequence":"additional","affiliation":[{"name":"ApconiX  Alderley Edge UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1134-2869","authenticated-orcid":false,"given":"Rebecca","family":"Jensen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Centre for Drug Safety Science University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gibson","sequence":"additional","affiliation":[{"name":"Murdoch University Institute for Immunology &amp; Infectious Diseases  Perth Western Australia Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew S.","family":"Krantz","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Ardern\u2010Jones","sequence":"additional","affiliation":[{"name":"Clinical Experimental Sciences University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton General Hospital  Southampton UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth J.","family":"Phillips","sequence":"additional","affiliation":[{"name":"Vanderbilt Institute for Infection, Immunology and Inflammation Vanderbilt University  Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munir","family":"Pirmohamed","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Centre for Drug Safety Science University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amy E.","family":"Chadwick","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and Therapeutics, Centre for Drug Safety Science University of Liverpool  Liverpool UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Betts","sequence":"additional","affiliation":[{"name":"Clinical Pharmacology &amp; 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