{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T08:36:17Z","timestamp":1785832577875,"version":"3.56.0"},"reference-count":46,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T00:00:00Z","timestamp":1748304000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100018645","name":"MRC","doi-asserted-by":"publisher","award":["MR\/X00094X\/1"],"award-info":[{"award-number":["MR\/X00094X\/1"]}],"id":[{"id":"10.13039\/100018645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vancomycin, a glycopeptide antibiotic used to treat severe Gram-positive bacterial infections, is associated with the development of drug reaction with eosinophilia and systemic symptoms (DRESS) in individuals expressing HLA-A*32:01. Previous studies have identified the potential role of T-cells using HLA-A*32:01-positive healthy donor models. However, DRESS pathogenesis remains poorly defined, and a deeper mechanistic understanding is required to aid the diagnosis and prediction of vancomycin-induced DRESS. The present study aims to elucidate CD4+ and CD8+ T-cell involvement within the pathogenesis of vancomycin-induced DRESS following the isolation and functional study of cloned T-cells from hypersensitive patients. CD4+ and CD8+ vancomycin-responsive T-cell clones (TCCs) were generated by serial dilution from peripheral blood mononuclear cells collected from suspected vancomycin-DRESS patients. Functionality of drug-responsive TCCs was assessed using T-cell proliferation ([3H]-thymidine). Cytokine analysis was performed using intracellular cytokine staining, enzyme-linked immunospot assay, and LEGENDplex immunoassays. Vancomycin-responsive TCCs expressing CD4+ and CD8+ phenotypes were successfully generated from suspected vancomycin-DRESS patients (n\u2009=\u20093). CD45RO+ memory T-cells were the primary activated population, with both CD4+ and CD8+ T-cells associated with the release of IFN-\u03b3, IL-5, IL-13, granzyme B, and perforin. Vancomycin-responsive CD4+ and CD8+ T-cells are activated by direct, pharmacological interactions, with antigen presentation possible through HLA class I and HLA class II molecules. This study provides in vitro evidence for the dual role of antigen-specific CD4+ and CD8+ T-cells within the pathogenesis of vancomycin-induced DRESS. This has been demonstrated following the generation of cloned T-cells with strong vancomycin specificity from patients presenting with vancomycin-DRESS and positive for expression of HLA-A*32:01.<\/jats:p>","DOI":"10.1093\/toxsci\/kfaf074","type":"journal-article","created":{"date-parts":[[2025,5,27]],"date-time":"2025-05-27T14:21:43Z","timestamp":1748355703000},"page":"420-432","source":"Crossref","is-referenced-by-count":5,"title":["Elucidating CD4+ and CD8+ T-cell involvement in patients with vancomycin-induced DRESS"],"prefix":"10.1093","volume":"206","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, The University of Liverpool , Liverpool L69 3GE,","place":["United 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and Therapeutics, Centre for Drug Safety Science, The University of Liverpool , Liverpool L69 3GE,","place":["United Kingdom"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Gibson","sequence":"additional","affiliation":[{"name":"Institute for Immunology & Infectious Diseases, Murdoch University , Perth 6150,","place":["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, TN 37232,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1466-2016","authenticated-orcid":false,"given":"Michael","family":"Ardern-Jones","sequence":"additional","affiliation":[{"name":"Clinical Experimental Sciences, University of Southampton Faculty of Medicine, Sir Henry Wellcome Laboratories, Southampton 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