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Due to self-reactivity, TVM cells are exposed to persistent antigenic stimulation, a condition known to induce T cell exhaustion. However, TVM cells do not exhibit characteristics similar to exhausted CD8 T (TEX) cells. Here, we tested the role of the UFL1, E3 ligase of the ufmylation pathway in TVM cells. We show that UFL1 prevents the acquisition of epigenetic, transcriptional, and phenotypic changes in TVM cells that are similar to TEX cells and thus promote their survival and function. UFL1-deficient TVM cells failed to protect mice against Listeria infection. Epigenetic analysis showed higher BATF activity in UFL1-deficient TVM cells. Deletion of BATF and not PD1 decreased inhibitory molecules expression and restored the survival and function of UFL1-deficient TVM cells. Our findings demonstrate a key role of UFL1 in inhibiting the exhaustion of TVM cells and promoting their survival and function.<\/jats:p>","DOI":"10.1093\/jimmun\/vkae042","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T15:44:06Z","timestamp":1740411846000},"page":"446-459","source":"Crossref","is-referenced-by-count":4,"title":["UFL1 promotes survival and function of virtual memory CD8 T cells"],"prefix":"10.1093","volume":"214","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6860-0561","authenticated-orcid":false,"given":"Brinda","family":"Bhatt","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United 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30912,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huabin","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8382-2613","authenticated-orcid":false,"given":"Andrew","family":"Wanna","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United 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Augusta, GA 30912,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian S","family":"Sheridan","sequence":"additional","affiliation":[{"name":"Center for Infectious Diseases, Stony Brook University , Stony Brook, NY,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Demetrius","family":"Moskophidis","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United States"]},{"name":"Georgia Cancer Center, Medical College of Georgia, Augusta University , Augusta, GA 30912,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-0982","authenticated-orcid":false,"given":"Honglin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Biology, Medical College of Georgia, 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