ArticleProceedings of the National Academy of Sciences of the United States of America2015
Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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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.
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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
22 citing papers in PubMed, 38 citations in OpenAlex.
- Article
- T Cell Development and Responses in Human Immune System Mice.Annual review of immunology · 2025Review
- Genetically corrected RAG2-SCID human hematopoietic stem cells restore V(D)J-recombinase and rescue lymphoid deficiency.Blood advances · 2024Article
- Gene therapy for inborn errors of immunity: past, present and future.Nature reviews. Immunology · 2023Review
- Co-Transplantation of Barcoded Lymphoid-Primed Multipotent (LMPP) and Common Lymphocyte (CLP) Progenitors Reveals a Major Contribution of LMPP to the Lymphoid Lineage.International journal of molecular sciences · 2023Article
- The Reconstitution Dynamics of Cultivated Hematopoietic Stem Cells and Progenitors Is Independent of Age.International journal of molecular sciences · 2022Article
- Review
- Interrogation of clonal tracking data usingNature computational science · 2021Article
- Long-term lymphoid progenitors independently sustain naïve T and NK cell production in humans.Nature communications · 2021Article
- An adequate human T cell repertoire from a single T cell progenitor: Lessons from an experiment of nature.EBioMedicine · 2020Article
- Long-term robustness of a T-cell system emerging from somatic rescue of a genetic block in T-cell development.EBioMedicine · 2020Article
- Understanding Normal and Malignant Human Hematopoiesis Using Next-Generation Humanized Mice.Trends in immunology · 2020Review
- The clonal repopulation of HSPC gene modified with anti-HIV-1 RNAi is not affected by preexisting HIV-1 infection.Science advances · 2020Article
- Advances in Human Immune System Mouse Models for Studying Human Hematopoiesis and Cancer Immunotherapy.Frontiers in immunology · 2020Review
- The development of human immune system mice and their use to study tolerance and autoimmunity.Journal of translational autoimmunity · 2019Review
- Development of anFuture science OA · 2019Article
- Generation and function of progenitor T cells from StemRegenin-1-expanded CD34+ human hematopoietic progenitor cells.Blood advances · 2019Article
- T Lymphocyte Development and Activation in Humanized Mouse Model.Development & reproduction · 2019Review
- Geographic clonal tracking in macaques provides insights into HSPC migration and differentiation.The Journal of experimental medicine · 2018Article
- The development of T cells from stem cells in mice and humans.Future science OA · 2017Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The fate and numbers of hematopoietic stem cells (HSC) and their progeny that seed the thymus constitute a fundamental question with important clinical implications. HSC transplantation is often complicated by limited T-cell reconstitution, especially when HSC from umbilical cord blood are used. Attempts to improve immune reconstitution have until now been unsuccessful, underscoring the need for better insight into thymic reconstitution. Here we made use of the NOD-SCID-IL-2Rγ(-/-) xenograft model and lentiviral cellular barcoding of human HSCs to study T-cell development in the thymus at a clonal level. Barcoded HSCs showed robust (>80% human chimerism) and reproducible myeloid and lymphoid engraftment, with T cells arising 12 wk after transplantation. A very limited number of HSC clones (<10) repopulated the xenografted thymus, with further restriction of the number of clones during subsequent development. Nevertheless, T-cell receptor rearrangements were polyclonal and showed a diverse repertoire, demonstrating that a multitude of T-lymphocyte clones can develop from a single HSC clone. Our data imply that intrathymic clonal fitness is important during T-cell development. As a consequence, immune incompetence after HSC transplantation is not related to the transplantation of limited numbers of HSC but to intrathymic events.
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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.