Development of a diverse human T-cell repertoire despite stringent restriction of hematopoietic clonality in the thymus

Martijn H. Brugman, Anna-Sophia Wiekmeijer, Marja van Eggermond, Ingrid Wolvers-Tettero, Anton W. Langerak, Edwin F. E. de Haas, Leonid V. Bystrykh, Jon J. van Rood*, Gerald de Haan, Willem E. Fibbe, Frank J. T. Staal

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    27 Citations (Scopus)
    413 Downloads (Pure)

    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-2R gamma(-/-) 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 (

    Original languageEnglish
    Pages (from-to)E6020-E6027
    Number of pages8
    JournalProceedings of the National Academy of Science of the United States of America
    Volume112
    Issue number44
    DOIs
    Publication statusPublished - 3-Nov-2015

    Keywords

    • thymus
    • T-cell receptor
    • hematopoietic stem cell
    • T-cell development
    • T lymphocyte
    • NONINHERITED MATERNAL ANTIGENS
    • UMBILICAL-CORD BLOOD
    • IMMUNE RECONSTITUTION
    • STEM-CELLS
    • TRANSPLANTATION
    • MICE
    • THYMOPOIESIS
    • DYNAMICS
    • GROWTH
    • QUANTIFICATION

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