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Here, we demonstrated that overexpression of Tle1, Tle3, and Tle4 improves the proliferation of antigen-specific effector CD8+ T cells during both acute and chronic viral infections. Notably, overexpression of Tle3 and Tle4, but not Tle1, augmented secondary responses of memory CD8+ T cells in the context of acute viral infection. Tle1-overexpressing CD8+ T cells displayed enhanced TCR signal strength, accompanied by elevated expression of immunoinhibitory receptors such as PD-1 and LAG-3. Transcriptome analyses and genome-wide binding profiles suggested that Tle1 and Tle3 cooperate with multiple transcription factors, including members of the Ets, AP-1, and Runx families, to drive expression of genes involved in the activation and maintenance of antigen-specific CD8+ T cell responses. Notably, Tle1 overexpression improves cytotoxic T lymphocyte (CTL) responses to PD-1\/PD-L1 blockade during chronic viral infection. Tle1 was found to enhance TCR signalling and the expression of immunoinhibitory receptors through repression of TCF-1, whereas its effect on effector CD8+ T cell proliferation occurred independently of TCF-1. These findings revealed the regulatory roles of Tle proteins in orchestrating transcription factor networks that govern CD8+ T cell differentiation during viral infections.<\/jats:p>","DOI":"10.1093\/intimm\/dxag001","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T12:46:42Z","timestamp":1769690802000},"page":"357-370","source":"Crossref","is-referenced-by-count":0,"title":["Overexpression of the transcriptional corepressor Tle1 enhances effector proliferation of CD8+ T cells during acute and chronic viral infections"],"prefix":"10.1093","volume":"38","author":[{"given":"Ryotaro","family":"Shiga","sequence":"first","affiliation":[{"name":"Department of Molecular Genetics, Graduate School of Medical Sciences, Kanazawa University , Kanazawa, Ishikawa 920-8640 ,","place":["Japan"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sotaro","family":"Fujisawa","sequence":"additional","affiliation":[{"name":"Department of Molecular Genetics, 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