ArticleThe Journal of experimental medicine1996
Differentiation and stability of T helper 1 and 2 cells derived from naive human neonatal CD4+ T cells, analyzed at the single-cell level.
Article in The Journal of experimental medicine, 1996. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 274 citations in OpenAlex.
- Pooled it
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- Clinical and Pathophysiological Tangles Between Allergy and Autoimmunity: Deconstructing an Old Dichotomic Paradigm.Clinical reviews in allergy & immunology · 2025Review
- The Possible Roles of IL-4/IL-13 in the Development of Eosinophil-Predominant Severe Asthma.Biomolecules · 2024Review
- Design of Glycoengineered IL-4 Antagonists Employing Chemical and Biosynthetic Glycosylation.ACS omega · 2023Article
- Review
- Profile of T and B lymphocytes in individuals resistant to Schistosoma mansoni infection.Parasitology research · 2022Article
- Article
- Combined Immunotherapy With Belatacept and BTLA Overexpression Attenuates Acute Rejection Following Kidney Transplantation.Frontiers in immunology · 2021Article
- Histone H3K27me3 demethylases regulate human Th17 cell development and effector functions by impacting on metabolism.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Preclinical study of safety and immunogenicity of combined rubella and human papillomavirus vaccines: Towards enhancing vaccination uptake rates in developing countries.Papillomavirus research (Amsterdam, Netherlands) · 2019Article
- Pre-conception maternal helminth infection transfers via nursing long-lasting cellular immunity against helminths to offspring.Science advances · 2019Article
- Increased CD4Clinical epigenetics · 2018Article
- IL-1β Production by Intermediate Monocytes Is Associated with Immunopathology in Cutaneous Leishmaniasis.The Journal of investigative dermatology · 2018Article
- Modeling Human Antitumor ResponsesFrontiers in immunology · 2018Review
- Dedicator of cytokinesis 8-deficient CD4The Journal of allergy and clinical immunology · 2017Article
- Increasing JAK/STAT Signaling Function of Infant CD4Frontiers in pediatrics · 2017Article
- Atopy and autoimmune thyroid diseases: melatonin can be useful?Italian journal of pediatrics · 2016Review
- Unique and shared signaling pathways cooperate to regulate the differentiation of human CD4+ T cells into distinct effector subsets.The Journal of experimental medicine · 2016Article
- Seasonal Association of Immune Thrombocytopenia in Adults.Balkan medical journal · 2015Article
2 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
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The development of CD4+ T helper (Th) type 1 and 2 cells is essential for the eradication of pathogens, but can also be responsible for various pathological disorders. Therefore, modulation of Th cell differentiation may have clinical utility in the treatment of human disease. Here, we show that interleukin (IL) 12 and IL-4 directly induce human neonatal CD4- T cells, activated via CD3 and CD28, to differentiate into Th1 and Th2 subsets. In contrast, IL-13, which shares many biological activities with IL-4, failed to induce T cell differentiation, consistent with the observation that human T cells do not express IL-13 receptors. Both the IL-12-induced Th1 subset and the IL-4-induced Th2 subset produce large quantities of IL-10, confirming that human IL-10 is not a typical human Th2 cytokine. Interestingly, IL-4-driven Th2 cell differentiation was completely prevented by an IL-4 mutant protein (IL-4.Y124D), indicating that this molecule acts as a strong IL-4 receptor antagonist. Analysis of single T cells producing interferon gamma or IL-4 revealed that induction of Th1 cell differentiation occurred rapidly and required only 4 d of priming of the neonatal CD4+ T cells in the presence of IL-12. The IL-12-induced Th1 cell phenotype was stable and was not significantly affected when repeatedly stimulated in the presence of recombinant IL-4. In contrast, the differentiation of Th2 cells occurred slowly and required not only 6 d of priming, but also additional restimulation of the primed CD4+ T cells in the presence of IL-4. Moreover, IL-4-induced Th2 cell phenotypes were not stable and could rapidly be reverted into a population predominantly containing Th0 and Th1 cells, after a single restimulation in the presence of IL-12. The observed differences in stability of IL-12- and IL-4-induced human Th1 and Th2 subsets, respectively, may have implications for cytokine-based therapies of chronic disease.
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