ArticleJournal of immunology (Baltimore, Md. : 1950)2014
Differential requirement for IL-2 and IL-15 during bifurcated development of thymic regulatory T cells.
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 43 papers.
What it found
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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.
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Who cites it
43 citing papers in PubMed, 69 citations in OpenAlex.
- TCR signal strength during positive selection shapes CD25 expression patterns on thymically derived regulatory T cells.bioRxiv : the preprint server for biology · 2026Article
- [Guardians of Immune Tolerance: Regulatory T Cells].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Review
- A linear ontogeny accounts for the development of naive, memory, and tumor-infiltrating regulatory T cells in mice.Science immunology · 2025Article
- Review
- Interleukin-2 receptor signaling acts as a checkpoint that influences the distribution of regulatory T cell subsets.iScience · 2024Article
- Adjusting to self in the thymus: CD4 versus CD8 lineage commitment and regulatory T cell development.The Journal of experimental medicine · 2024Review
- Lymphotoxin limits Foxp3Nature communications · 2024Article
- Curcumin as a regulator of Th17 cells: Unveiling the mechanisms.Food chemistry. Molecular sciences · 2024Review
- MicroRNAs targeting TGF-β signaling exacerbate central nervous system autoimmunity by disrupting regulatory T cell development and function.European journal of immunology · 2024Article
- Interleukin-2 signaling in the regulation of T cell biology in autoimmunity and cancer.Immunity · 2024Review
- DNA demethylation fine-tunes IL-2 production during thymic regulatory T cell differentiation.EMBO reports · 2023Article
- How autoreactive thymocytes differentiate into regulatory versus effector CD4Nature immunology · 2023Article
- The protective and pathogenic role of Th17 cell plasticity and function in the tumor microenvironment.Frontiers in immunology · 2023Review
- Recirculating Foxp3Cellular and molecular life sciences : CMLS · 2022Article
- IL-2 and IL-15 drive intrathymic development of distinct periphery-seeding CD4Frontiers in immunology · 2022Article
- Role and Function of Regulatory T Cell in Chronic Rhinosinusitis with Nasal Polyposis.Journal of immunology research · 2022Review
- Modeling the Dynamics of T-Cell Development in the Thymus.Entropy (Basel, Switzerland) · 2021Review
- Next-generation cytokines for cancer immunotherapy.Antibody therapeutics · 2021Review
- The Roles of Immunoregulatory Networks in Severe Drug Hypersensitivity.Frontiers in immunology · 2021Review
- Factors that influence the thymic selection of CD8αα intraepithelial lymphocytes.Mucosal immunology · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The developmental pathways of regulatory T cells (T(reg)) generation in the thymus are not fully understood. In this study, we reconstituted thymic development of Zap70-deficient thymocytes with a tetracycline-inducible Zap70 transgene to allow temporal dissection of T(reg) development. We find that T(reg) develop with distinctive kinetics, first appearing by day 4 among CD4 single-positive (SP) thymocytes. Accepted models of CD25(+)Foxp3(+) T(reg) selection suggest development via CD25(+)Foxp3(-) CD4 SP precursors. In contrast, our kinetic analysis revealed the presence of abundant CD25(-)Foxp3(+) cells that are highly efficient at maturing to CD25(+)Foxp3(+) cells in response to IL-2. CD25(-)Foxp3(+) cells more closely resembled mature T(reg) both with respect to kinetics of development and avidity for self-peptide MHC. These population also exhibited distinct requirements for cytokines during their development. CD25(-)Foxp3(+) cells were IL-15 dependent, whereas generation of CD25(+)Foxp3(+) specifically required IL-2. Finally, we found that IL-2 and IL-15 arose from distinct sources in vivo. IL-15 was of stromal origin, whereas IL-2 was of exclusively from hemopoetic cells that depended on intact CD4 lineage development but not either Ag-experienced or NKT cells.
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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.