ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Ikaros imposes a barrier to CD8+ T cell differentiation by restricting autocrine IL-2 production.
Article in Journal of immunology (Baltimore, Md. : 1950), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
32 citing papers in PubMed, 52 citations in OpenAlex.
- First-in-Human, Single- and Multiple-Ascending-Dose Studies in Healthy Subjects to Assess Pharmacokinetics, Pharmacodynamics, and Safety/Tolerability of Iberdomide, a Novel Cereblon E3 Ligase Modulator.Clinical pharmacology in drug development · 2021Trial
- Understanding the dual role of granulocyte-macrophage colony-stimulating factor in the lung cancer tumor microenvironment and its therapeutic implications.Translational lung cancer research · 2026Review
- Imbalance of stem-like and effector T cell states in children with early type 1 diabetes across conventional and regulatory subsets.Nature communications · 2025Article
- Defining molecular circuits of CD8+ T cell responses in tissues during latent viral infection.The Journal of experimental medicine · 2025Article
- Polyfunctional CD8Molecular oncology · 2025Article
- Degradation of IKZF1 prevents epigenetic progression of T cell exhaustion in an antigen-specific assay.Cell reports. Medicine · 2024Article
- LIM-domain-only 4 (LMO4) enhances CD8Signal transduction and targeted therapy · 2024Article
- Article
- TIM-3, LAG-3, or 2B4 gene disruptions increase the anti-tumor response of engineered T cells.Frontiers in immunology · 2024Article
- Role of tumor-associated neutrophils in lung cancer (Review).Oncology letters · 2023Review
- Optimal CD8Nature communications · 2022Article
- Combination Immune Checkpoint Blockade Enhances IL-2 and CD107a Production from HIV-Specific T Cells Ex Vivo in People Living with HIV on Antiretroviral Therapy.Journal of immunology (Baltimore, Md. : 1950) · 2022Article
- Keeping Myeloma in Check: The Past, Present and Future of Immunotherapy in Multiple Myeloma.Cancers · 2021Review
- Biological and Translational Considerations regarding the Recent Therapeutic Successes and Upcoming Challenges for Multiple Myeloma.Cold Spring Harbor perspectives in medicine · 2021Review
- Established and emergent roles for Ikaros transcription factors in lymphoid cell development and function.Immunological reviews · 2021Review
- Article
- Coexpression of FOXP3 and a Helios isoform enhances the effectiveness of human engineered regulatory T cells.Blood advances · 2020Article
- CXCR3 Identifies Human Naive CD8Journal of immunology (Baltimore, Md. : 1950) · 2019Article
- Function of Human Tumor-Infiltrating Lymphocytes in Early-Stage Non-Small Cell Lung Cancer.Cancer immunology research · 2019Article
- Assessing the Functional Relevance of Variants in theFrontiers in immunology · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Naive CD4(+) T cells require signals from the TCR and CD28 to produce IL-2, expand, and differentiate. However, these same signals are not sufficient to induce autocrine IL-2 production by naive CD8(+) T cells, which require cytokines provided by other cell types to drive their differentiation. The basis for failed autocrine IL-2 production by activated CD8(+) cells is unclear. We find that Ikaros, a transcriptional repressor that silences IL-2 in anergic CD4(+) T cells, also restricts autocrine IL-2 production by CD8(+) T cells. We find that CD8(+) T cell activation in vitro in the absence of exogenous cytokines and CD4 help leads to marked induction of Ikaros, a known repressor of the Il2 gene. Naive murine CD8 T cells haplo-insufficient for Ikzf1 failed to upregulate Ikaros, produced autocrine IL-2, and differentiated in an IL-2-dependent manner into IFN-γ-producing CTLs in response to TCR/CD28 stimulation alone. Furthermore, Ikzf1 haplo-insufficient CD8(+) T cells were more effective at controlling Listeria infection and B16 melanoma growth in vivo, and they could provide help to neighboring, non-IL-2-producing cells to differentiate into IFN-γ-producing effectors. Therefore, by repressing autocrine IL-2 production, Ikaros ensures that naive CD8(+) T cells remain dependent on licensing by APCs and CD4(+) T cells, and it may therefore act as a cell-intrinsic safeguard against inappropriate CTL differentiation and immunopathology.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.