ArticleThe Journal of experimental medicine2013
Helios marks strongly autoreactive CD4+ T cells in two major waves of thymic deletion distinguished by induction of PD-1 or NF-κB.
Article in The Journal of experimental medicine, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 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
115 citing papers in PubMed, 167 citations in OpenAlex.
- ZFP36L1 and ZFP36L2 cooperatively regulate thymic epithelial cell function to prevent early-onset thymic involution.Cell death and differentiation · 2026Article
- Improved conditioning for hematopoietic chimerism induces islet tolerance to cure diabetes.JCI insight · 2026Article
- Perp Deficiency Induces Defective Negative Selection and Autoimmune Arthritis in Aged Mice.Aging cell · 2026Article
- The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct thymocyte cell types.Nature immunology · 2026Article
- Multifaceted regulation of thymic tolerance by pattern recognition cascades.Frontiers in immunology · 2026Review
- Integrin CD103 reveals a distinct developmental pathway of autoreactive thymocytes in TCR transgenic mice.Nature communications · 2025Article
- Nr4a1 and Nr4a3 redundantly control clonal deletion and contribute to an anergy-like transcriptome in auto-reactive thymocytes to impose tolerance in mice.Nature communications · 2025Article
- Helios-Illuminating the way for lymphocyte self-control.Immunology · 2025Review
- Physiological and pathogenic T cell autoreactivity converge in type 1 diabetes.Nature communications · 2024Article
- Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling.Science advances · 2024Article
- Stabilization of β-Catenin Directs HEB to Limit Thymic Selection.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Foxo3 regulates cortical and medullary thymic epithelial cell homeostasis with implications in T cell development.Cell death & disease · 2024Article
- IKK2 controls the inflammatory potential of tissue-resident regulatory T cells in a murine gain of function model.Nature communications · 2024Article
- Mitochondrial protein C15ORF48 is a stress-independent inducer of autophagy that regulates oxidative stress and autoimmunity.Nature communications · 2024Article
- Expression of the transcription factor Klf6 by thymic epithelial cells is required for thymus development.Science advances · 2023Article
- Single-cell multiomic analysis of thymocyte development reveals drivers of CD4Nature immunology · 2023Article
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- I-ANature immunology · 2023Article
- LAMP2 regulates autophagy in the thymic epithelium and thymic stroma-dependent CD4 T cell development.Autophagy · 2023Article
- Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity.iScience · 2023Article
55 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Acquisition of self-tolerance in the thymus requires T cells to discriminate strong versus weak T cell receptor binding by self-peptide-MHC complexes. We find this discrimination is reported by expression of the transcription factor Helios, which is induced during negative selection but decreases during positive selection. Helios and the proapoptotic protein Bim were coinduced in 55% of nascent CCR7(-) CD4(+) CD69(+) thymocytes. These were short-lived cells that up-regulated PD-1 and down-regulated CD4 and CD8 during Bim-dependent apoptosis. Helios and Bim were also coinduced at the subsequent CCR7(+) CD4(+) CD69(+) CD8(-) stage, and this second wave of Bim-dependent negative selection involved 20% of nascent cells. Unlike CCR7(-) counterparts, Helios(+) CCR7(+) CD4(+) cells mount a concurrent Card11- and c-Rel-dependent activation response that opposes Bim-mediated apoptosis. This "hollow" activation response consists of many NF-κB target genes but lacks key growth mediators like IL-2 and Myc, and the thymocytes were not induced to proliferate. These findings identify Helios as the first marker known to diverge during positive and negative selection of thymocytes and reveal the extent, stage, and molecular nature of two distinct waves of clonal deletion in the normal thymus.
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.