{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T14:17:16Z","timestamp":1787062636429,"version":"build-2736575974"},"reference-count":88,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Allergy"],"published-print":{"date-parts":[[2023,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Eosinophilia is a common finding in drug hypersensitivity reactions (DHR). Its cause is unclear, as neither antigen\/allergen\u2010driven inflammation nor clonal expansion is involved. Most delayed\u2010DHRs are due to p\u2010i (\n                    <jats:bold>p<\/jats:bold>\n                    harmacologic interaction of drugs with\n                    <jats:bold>i<\/jats:bold>\n                    mmune receptors). These are off\u2010target activities of drugs with immune receptors that result in various types of T\u2010cell stimulation, some of which involve excessive IL\u20105 production. Functional and phenotypic studies of T\u2010cell clones and their TCR\u2010transfected hybridoma cell lines revealed that some p\u2010i\u2010induced drug stimulations occur without CD4\/ CD8 co\u2010receptor engagement. The CD4\/CD8 co\u2010receptors link Lck (lymphocyte\u2010specific protein tyrosine kinase) and LAT (linker for activation of T cells) to the TCR. Alteration of Lck or LAT can result in a TCR signalosome with enhanced IL\u20105 production. Thus, if a more affine TCR\u2010[drug\/peptide\/HLA] interaction allows bypassing the CD4 co\u2010receptor, a modified Lck\/LAT activation may lead to a TCR signalosome with elevated IL\u20105 production. This \u201cIL\u20105\u2010TCR\u2010signalosome\u201d hypothesis could also explain eosinophilia in superantigen or allo\u2010stimulation (graft\u2010versus\u2010host disease), in which evasion of CD4\/CD8 co\u2010receptors has also been described. It may open new therapeutic possibilities in certain eosinophilic diseases by directly targeting the IL\u20105\u2010TCR signalosome.\n                  <\/jats:p>","DOI":"10.1111\/all.15795","type":"journal-article","created":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T08:10:20Z","timestamp":1688371820000},"page":"2596-2605","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Drug hypersensitivity and eosinophilia: The decisive role of p\u2010i stimulation"],"prefix":"10.1111","volume":"78","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8117-359X","authenticated-orcid":false,"given":"Werner J.","family":"Pichler","sequence":"first","affiliation":[{"name":"ADR\u2010AC GmbH  Bern 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