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Adv."],"published-print":{"date-parts":[[2026,9,18]]},"abstract":"<jats:p>\n                    Na\u00efve T cells maintain quiescence yet must respond rapidly to antigens, but how they prime this capacity is unclear. We identify histone variant H2A.Z as a key regulator of an epigenetic training program that licenses quiescent na\u00efve CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells for future activation. H2A.Z deficiency disrupts na\u00efve T cell homeostasis and effector responses. Multiomics reveals that H2A.Z is selectively deposited at oxidative phosphorylation (OXPHOS) gene promoters in quiescent na\u00efve CD8\n                    <jats:sup>+<\/jats:sup>\n                    T cells, priming the chromatin for rapid transcriptional induction. This training is developmentally instructed by tonic interleukin-7 (IL-7) signaling and regulated by transcription factor GABP\u03b1. Age-related decline in IL-7 signaling reduces H2A.Z occupancy and impairs T cell activation, while IL-7 supplementation or enforced H2A.Z expression rescues this defect. H2A.Z overexpression also enhances chimeric antigen receptor T cell stemness and antitumor efficacy. Our work defines an IL-7R\u2013GABP\u03b1\u2013H2A.Z\u2013OXPHOS axis that epigenetically establishes metabolic and functional fitness in quiescent T cells, offering insights for immunotherapy targeting ageing and tumors.\n                  <\/jats:p>","DOI":"10.1126\/sciadv.aee8251","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T18:04:04Z","timestamp":1789754644000},"update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":0,"title":["Epigenetic training licenses na\u00efve CD8\n                    <sup>+<\/sup>\n                    T cell metabolic fitness and function"],"prefix":"10.1126","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-8915-3778","authenticated-orcid":true,"given":"Mengjie","family":"Lv","sequence":"first","affiliation":[{"name":"CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, 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