ArticleProceedings of the National Academy of Sciences of the United States of America2013
Murine thymic selection quantified using a unique method to capture deleted T cells.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 118 papers.
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Who cites it
118 citing papers in PubMed, 180 citations in OpenAlex.
- Article
- The differentiation and function of heterogeneous thymic dendritic cell subsets require signals provided by distinct thymocyte cell types.Nature immunology · 2026Article
- Tumor-associated NK Cells Regulate Distinct CD8+ T-cell Differentiation Program in Cancer and Contribute to Resistance against Immune Checkpoint Blockers.Cancer discovery · 2025Article
- Activated STING in the thymic epithelium alters T cell development and selection leading to autoimmunity.The Journal of clinical investigation · 2025Article
- Basic interactions responsible for thymus function explain the convoluted medulla shape.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Immune tolerance to foreign antigens in the intestine: mechanisms mediated by CD4＋ T cells.BMB reports · 2025Review
- 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
- A multidimensional toolkit for elucidating temporal trajectories in cell development in vivo.Development (Cambridge, England) · 2024Article
- The partitioning of TCR repertoires by thymic selection.The Journal of experimental medicine · 2024Review
- Skewed epithelial cell differentiation and premature aging of the thymus in the absence of vitamin D signaling.Science advances · 2024Article
- Article
- Is the exquisite specificity of lymphocytes generated by thymic selection or due to evolution?Frontiers in immunology · 2024Article
- BATF represses BIM to sustain tolerant T cells in the periphery.The Journal of experimental medicine · 2023Article
- What's the Catch? The Significance of Catch Bonds in T Cell Activation.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- CCR4 and CCR7 differentially regulate thymocyte localization with distinct outcomes for central tolerance.eLife · 2023Article
- A single-amino acid substitution in the adaptor LAT accelerates TCR proofreading kinetics and alters T-cell selection, maintenance and function.Nature immunology · 2023Article
- Metabolic adaptation supports enhanced macrophage efferocytosis in limited-oxygen environments.Cell metabolism · 2023Article
- Article
- Activation-induced cytidine deaminase expression by thymic B cells promotes T-cell tolerance and limits autoimmunity.iScience · 2023Article
- Article
58 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Thymic positive and negative selection events generate a T-cell repertoire that is MHC restricted and self-tolerant. The number of T cells undergoing positive and negative selection in normal mice has never been firmly established. We generated mice that lack the proapoptotic molecule Bim (bcl2l11) together with a Nur77(GFP) transgene, which allowed the identification and enumeration of T cells that would normally undergo clonal deletion. Using this method, we report the striking observation that six times more cells undergo negative selection than complete positive selection. Seventy-five percent of the negatively selected cells are deleted at the double positive stage in the thymic cortex, compared with 25% at the single positive stage in the medulla. The fact that more thymocytes are highly reactive to MHC than are weakly reactive is inconsistent with a random model of recognition and suggests that T-cell recognition is MHC biased. Furthermore, Bim(-/-) mice had an increased number of GFP(hi) cells in the peripheral lymphoid tissue and a corresponding increase in antigen experienced or anergic cell phenotype. Our data also show that the CD4+ T cells that are clonally deleted experienced only slightly stronger T-cell receptor signaling than those that developed into regulatory T cells.
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