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We have recently shown that virus\u2010experienced innate acting T (T\n                    <jats:sub>IA<\/jats:sub>\n                    ) cells can modulate infectious or autoimmune diseases through TCR\u2010independent IFN\u2010\u03b3 production. However, how these cells arise remains unclear. Here, we show that CD4 T\n                    <jats:sub>IA<\/jats:sub>\n                    cells are present in various disease settings hinting towards a disease\u2010agnostic nature. TCR stimulation and CD28 co\u2010stimulation are sufficient to induce na\u00efve murine and human CD4 T cells to become capable of cytokine\u2010mediated, TCR\u2010independent IFN\u2010\u03b3 responses. In true T\n                    <jats:sub>IA<\/jats:sub>\n                    fashion, adoptive transfer of in vitro\u2010induced T\n                    <jats:sub>IA<\/jats:sub>\n                    cells in mice yielded a TCR\u2010independent IFN\u2010\u03b3 response during the innate phase of a\n                    <jats:italic>Legionella pneumophila<\/jats:italic>\n                    infection. Our data thus shows that CD4 T\n                    <jats:sub>IA<\/jats:sub>\n                    cells are more ubiquitous than anticipated and could therefore be involved in more settings than expected.\n                  <\/jats:p>","DOI":"10.1002\/eji.70054","type":"journal-article","created":{"date-parts":[[2025,9,9]],"date-time":"2025-09-09T13:17:29Z","timestamp":1757423849000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["CD4 T Cells Acquire Innate Capability Upon Classical T Cell Activation"],"prefix":"10.1002","volume":"55","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0844-1276","authenticated-orcid":false,"given":"Nima","family":"Yassini","sequence":"first","affiliation":[{"name":"Department of Quantitative Biomedicine University of Zurich  Zurich 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