ArticleThe Journal of experimental medicine2015
The transcription factors ZEB2 and T-bet cooperate to program cytotoxic T cell terminal differentiation in response to LCMV viral infection.
Article in The Journal of experimental medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 190 papers.
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190 citing papers in PubMed, 272 citations in OpenAlex.
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- ID2 secures cDC1 specification by antagonizing E proteins at a pleiotropic Zeb2 enhancer.Nature immunology · 2026Article
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- Functions and features of circulating memory T cells.Immunity · 2026Review
- KLF2 overrides the resident memory CD8 T cell differentiation program, in opposition to KLF3.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- An early burst of cytokine production before the first cell division influences CD8 T cell differentiation.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- A distinct subset of stem-cell memory is poised for the cytotoxicity program in CD4Science advances · 2026Article
- How the wild things are: comparative T cell phenotyping and memory T cell identification in wild boar and domestic pigs.Frontiers in immunology · 2026Article
- Peripheral γδ T-cell remodeling in psoriasis is associated with effector-biased transcriptional organization and reduced representation of a circulatingFrontiers in immunology · 2026Article
- Senescent CD8 T Effector Memory Cells are Functionally Impaired, Enriched in Aging and Disease, and a Barrier to Immunotherapy.bioRxiv : the preprint server for biology · 2025Article
- Aging-associated transcriptional programs in T cells signify constituents of TGF-β signaling for immunosenescence.BMC biology · 2025Article
- High-Dimensional Single-Cell Analysis Reveals Coordinated Age-Dependent Neuroinflammatory Microglia-T cell Circuits in the Brain.bioRxiv : the preprint server for biology · 2025Article
- The transcription factor ZEB2 mediates the antitumor efficacy of tumor-infiltrating lymphocytes in non-small cell lung cancer.Cell death & disease · 2025Article
- Epigenetically Controlled ZEB2 Expression Promotes the Cytotoxic Potential of CMV-Specific CD8European journal of immunology · 2025Article
- Article
130 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
The transcription factor T-bet is critical for cytotoxic T lymphocyte (CTL) differentiation, but it is unclear how it operates in a graded manner in the formation of both terminal effector and memory precursor cells during viral infection. We find that, at high concentrations, T-bet induced expression of Zeb2 mRNA, which then triggered CTLs to adopt terminally differentiated states. ZEB2 and T-bet cooperate to switch on a terminal CTL differentiation program, while simultaneously repressing genes necessary for central memory CTL development. Chromatin immunoprecipitation sequencing showed that a large proportion of these genes were bound by T-bet, and this binding was altered by ZEB2 deficiency. Furthermore, T-bet overexpression could not fully bypass ZEB2 function. Thus, the coordinated actions of T-bet and ZEB2 outline a novel genetic pathway that forces commitment of CTLs to terminal differentiation, thereby restricting their memory cell potential.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.