ArticleProceedings of the National Academy of Sciences of the United States of America2004
Development of innate CD4+ alpha-chain variable gene segment 24 (Valpha24) natural killer T cells in the early human fetal thymus is regulated by IL-7.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 72 citations in OpenAlex.
- Expansion of CD1d-restricted NKT cells in patients with primary HIV-1 infection treated with interleukin-2.Blood · 2006Trial
- Human MAIT cells undergo clonal selection and expansion during thymic maturation and aging.Experimental & molecular medicine · 2025Article
- Unraveling the phenotypic states of human innate-like T cells: Comparative insights with conventional T cells and mouse models.Cell reports · 2024Article
- Single-cell transcriptomics reveal different maturation stages and sublineage commitment of human thymic invariant natural killer T cells.Journal of leukocyte biology · 2024Article
- Thymic development of human natural killer T cells: recent advances and implications for immunotherapy.Frontiers in immunology · 2024Review
- Unraveling the Phenotypic States of Human innate-like T Cells: Comparative Insights with Conventional T Cells and Mouse Models.bioRxiv : the preprint server for biology · 2023Article
- Aging unconventionally: γδ T cells, iNKT cells, and MAIT cells in aging.Seminars in immunology · 2023Review
- The early life education of the immune system: Moms, microbes and (missed) opportunities.Gut microbes · 2020Review
- IL-7 During Antigenic Stimulation Using Allogeneic Dendritic Cells Promotes Expansion of CD45RAFrontiers in immunology · 2020Article
- The peripheral differentiation of human natural killer T cells.Immunology and cell biology · 2019Article
- High Activation of γδ T Cells and the γδ2Frontiers in immunology · 2019Article
- Invariant NKT Cells and Control of the Thymus Medulla.Journal of immunology (Baltimore, Md. : 1950) · 2018Review
- Insights Into Mucosal-Associated Invariant T Cell Biology From Studies of Invariant Natural Killer T Cells.Frontiers in immunology · 2018Review
- The Role of Natural Killer T Cells in Cancer-A Phenotypical and Functional Approach.Frontiers in immunology · 2018Review
- Reciprocal Crosstalk between Dendritic Cells and Natural Killer T Cells: Mechanisms and Therapeutic Potential.Frontiers in immunology · 2017Review
- Expansion of highly activated invariant natural killer T cells with altered phenotype in acute dengue infection.Clinical and experimental immunology · 2016Article
- Regulation of NKT Cell Localization in Homeostasis and Infection.Frontiers in immunology · 2015Review
- Invariant natural killer T cells developing in the human fetus accumulate and mature in the small intestine.Mucosal immunology · 2014Article
- Invariant natural killer T (iNKT) cells in HAART-treated, HIV-positive patients with bone and cardiovascular impairment.PloS one · 2014Article
- Acquisition of innate-like microbial reactivity in mucosal tissues during human fetal MAIT-cell development.Nature communications · 2014Article
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Natural killer (NK) T cells are innate CD1d-restricted immune cells involved in regulation of immune tolerance, tumor immunity, and immunity to infectious pathogens. Human alpha-chain variable gene segment 24 (Valpha24) NK T cells exist in the periphery as two functionally distinct subsets: one CD4+ and one CD4- subset. However, the developmental pathway of human Valpha24 NK T cells is not well understood. Here, we show that Valpha24 NK T cells develop in the fetal thymus. The relative number of intrathymic NK T cell precursors decline in a linear manner with gestational age, and they are very rare in the neonatal thymus, indicating that these cells preferentially develop in the early fetal thymus. Their restriction element, CD1d, is expressed by a vast majority of thymocytes. A majority of intrathymic Valpha24 NK T cell progenitors are CD4+, whereas a minority are CD4/8(+/+). CD4+ Valpha24 NK T cell precursors show features of mature NK T cells, such as high levels of their semiinvariant T cell receptor and CD3 and some expression of CD161, whereas the CD4/8(+/+) precursors seem less mature. The cytokine IL-7 shows a biphasic effect on Valpha24 NK T cell progenitors in fetal thymic organ culture, with high doses driving proliferation of immature CD161-progenitors and low doses supporting survival and maturation. Thus, the data demonstrate that human Valpha24 NK T cells of the CD4+, but not the CD4-, subset develop in the early fetal thymus. Furthermore, data suggest an intrathymic pathway of CD4+ Valpha24 NK T cell development that is regulated by IL-7.
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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.