{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Murphy MK"],"funding":["NIAID NIH HHS"],"pagination":["2472-2488.e9"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC12717841"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["58(10)"],"pubmed_abstract":["During differentiation of CD8<sup>+</sup> T cells, the transcription factors TCF-1 and Blimp1 control progenitor and terminally differentiated states, respectively. Here, we examined the hierarchy and functional consequences of cross-regulation between these factors. We identified two Blimp1-bound cis-regulatory elements, Tcf7<sup>+22kb</sup> and Tcf7<sup>+17kb</sup>, that enforced Tcf7 silencing in a context-specific manner during both acute and chronic responses. Deletion of these elements decoupled Tcf7 repression from effector differentiation but did not rewire effector T cells to a memory state or prevent the acquisition of phenotypic hallmarks of exhaustion. However, combined ablation of Prdm1 and Tcf7 preserved a memory surface phenotype despite defects in secondary expansion. Thus, the anti-proliferative and pro-differentiative effects of Blimp1 in effector or exhausted CD8<sup>+</sup> T cells represent mechanistically distinct modules, wherein repression of Tcf7 limits proliferative capacity but not memory or progenitor specification."],"journal":["Immunity"],"pubmed_title":["The transcriptional repressor BLIMP1 enforces TCF-1-dependent and -independent restriction of the memory fate of CD8&lt;sup&gt;+&lt;/sup&gt; T cells."],"pmcid":["PMC12717841"],"funding_grant_id":["T32 AI007163","F31 AI174696","R01 AI134035","R01 AI170926","R01 AI130152","R01 AI176664"],"pubmed_authors":["Deffenbaugh JL","Egawa T","Colonna M","Chen AY","Hsiung S","Murphy MK","Pai J","Oltz EM","Daniel B","Ghoneim HE","Satpathy AT","Yousif A","Raju S","McCullen M","Wang Z"],"additional_accession":[]},"is_claimable":false,"name":"The transcriptional repressor BLIMP1 enforces TCF-1-dependent and -independent restriction of the memory fate of CD8&lt;sup&gt;+&lt;/sup&gt; T cells.","description":"During differentiation of CD8<sup>+</sup> T cells, the transcription factors TCF-1 and Blimp1 control progenitor and terminally differentiated states, respectively. Here, we examined the hierarchy and functional consequences of cross-regulation between these factors. We identified two Blimp1-bound cis-regulatory elements, Tcf7<sup>+22kb</sup> and Tcf7<sup>+17kb</sup>, that enforced Tcf7 silencing in a context-specific manner during both acute and chronic responses. Deletion of these elements decoupled Tcf7 repression from effector differentiation but did not rewire effector T cells to a memory state or prevent the acquisition of phenotypic hallmarks of exhaustion. However, combined ablation of Prdm1 and Tcf7 preserved a memory surface phenotype despite defects in secondary expansion. Thus, the anti-proliferative and pro-differentiative effects of Blimp1 in effector or exhausted CD8<sup>+</sup> T cells represent mechanistically distinct modules, wherein repression of Tcf7 limits proliferative capacity but not memory or progenitor specification.","dates":{"release":"2025-01-01T00:00:00Z","publication":"2025 Oct","modification":"2026-06-06T04:43:57.23Z","creation":"2026-05-25T03:12:13.574Z"},"accession":"S-EPMC12717841","cross_references":{"pubmed":["41043414"],"doi":["10.1016/j.immuni.2025.09.008"]}}