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With age, this quiescent state is lost and the CD8 T cell response to infection decreases. The factors regulating metabolic quiescence of CD8 T cells and how this regulation is lost during aging are not completely understood. Herein, we identify the transcription factor AFF3 as a regulator of metabolic quiescence in naive CD8 T cells. While naive AFF3-deficient CD8 T cells are more metabolically active prior to infection, they have reduced accumulation in response to viral infection, and this is correlated with a poor capacity to engage glycolysis. During aging in both murine and human CD8 T cells, AFF3 expression is decreased. In mice, this is associated with a loss of metabolic quiescence and reduced capacity to accumulate following infection. Our data highlight the role of metabolic regulation in CD8 T cell quiescence and identify a transcription factor that may be a target to reinvigorate CD8 T cell responses during aging.<\/jats:p>\n                  <jats:p>AFF3 is important to the function of cytotoxic T cells by regulating their metabolism. This protein is also important to prevent premature immune aging.<\/jats:p>","DOI":"10.1172\/jci.insight.207387","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T16:06:56Z","timestamp":1782230816000},"source":"Crossref","is-referenced-by-count":0,"title":["AFF3 maintains metabolic quiescence in naive CD8 T cells and prevents premature immune aging"],"prefix":"10.1172","volume":"11","author":[{"given":"Molly E.","family":"Lumnitzer","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology, IU Cooperative Center of Excellence in Hematology, and"},{"name":"IU Melvin and Bren Simon Comprehensive Cancer Center, Indiana University School of Medicine (IUSM), Indianapolis, Indiana, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie F.","family":"Valbon","sequence":"additional","affiliation":[{"name":"D\u00e9partement de Microbiologie, Immunologie et Infectiologie, Universit\u00e9 de Montr\u00e9al, 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