biostudies-literatureStrongin ZIntramural NIH HHSVetenskapsrådetNIAID NIH HHSU.S. Department of Health &amp; Human Services | NIH | National Institute of Allergy and Infectious DiseasesVetenskapsrådet (Swedish Research Council)U.S. Department of Health & Human Services | NIH | National Institute of Allergy and Infectious Diseases (NIAID)U.S. Department of Health & Human Services | National Institutes of Health (NIH)Division of Intramural Research, National Institute of Allergy and Infectious DiseasesDivision of Intramural Research, National Institute of Allergy and Infectious Diseases (Division of Intramural Research of the NIAID)U.S. Department of Health &amp; Human Services | NIH | National Cancer InstituteNCI NIH HHSU.S. Department of Health &amp; Human Services | National Institutes of HealthNIH HHS1245-1256https://www.ebi.ac.uk/biostudies/studies/S-EPMC11969417biostudies-literatureUnknown25(7)Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8⁺ T cell functions, which requires a deeper understanding of CD8⁺ T cells promoting HIV control. Here we identifiy an antigen-responsive TOX^hiTCF1⁺CD39⁺CD8⁺ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8⁺ T cells and proteomic analysis of purified CD8⁺ T cell subsets identified TOX^hiTCF1⁺CD39⁺CD8⁺ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOX<suNature immunologyDistinct SIV-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.PMC11969417UM1AI164562R56 AI150401P51 OD011132R01AI11637975N91019D00024R37 AI141258ZIA AI0010292023-00510P30 AI050409U42 OD011023R56AI150401R01 AI116379UM1 AI164562OD0267991ZIAAI001029S10 OD026799Raymond Marchand LGourves MTorres-Ruiz FLuna-Villalobos YAPaiardini MUrban EASaez-Cirion AHoang TNDeleage CHarper JPampena MBKissick HTDel Rio Estrada PMAvila-Rios SStrongin ZNguyen KBeusch CMReyes-Teran GSekaly RRahmberg ARGonzalez-Navarro MBosinger SETharp GKLapp SBrenchley JMKulpa DABetts MRCardenas MASilvestri GGordon DEfalseDistinct SIV-specific CD8&lt;sup&gt;+&lt;/sup&gt; T cells in the lymph node exhibit simultaneous effector and stem-like profiles and are associated with limited SIV persistence.Human immunodeficiency virus (HIV) cure efforts are increasingly focused on harnessing CD8⁺ T cell functions, which requires a deeper understanding of CD8⁺ T cells promoting HIV control. Here we identifiy an antigen-responsive TOX^hiTCF1⁺CD39⁺CD8⁺ T cell population with high expression of inhibitory receptors and low expression of canonical cytolytic molecules. Transcriptional analysis of simian immunodeficiency virus (SIV)-specific CD8⁺ T cells and proteomic analysis of purified CD8⁺ T cell subsets identified TOX^hiTCF1⁺CD39⁺CD8⁺ T cells as intermediate effectors that retained stem-like features with a lineage relationship with terminal effector T cells. TOX<su2024-01-01T00:00:00Z2024 Jul2026-06-02T19:19:16.739Z2026-04-19T03:13:31.966ZS-EPMC119694173888659210.1038/s41590-024-01875-0