Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-05

AUTHORS

Christopher S Seet, Chongbin He, Michael T Bethune, Suwen Li, Brent Chick, Eric H Gschweng, Yuhua Zhu, Kenneth Kim, Donald B Kohn, David Baltimore, Gay M Crooks, Amélie Montel-Hagen

ABSTRACT

Studies of human T cell development require robust model systems that recapitulate the full span of thymopoiesis, from hematopoietic stem and progenitor cells (HSPCs) through to mature T cells. Existing in vitro models induce T cell commitment from human HSPCs; however, differentiation into mature CD3+TCR-αβ+ single-positive CD8+ or CD4+ cells is limited. We describe here a serum-free, artificial thymic organoid (ATO) system that supports efficient and reproducible in vitro differentiation and positive selection of conventional human T cells from all sources of HSPCs. ATO-derived T cells exhibited mature naive phenotypes, a diverse T cell receptor (TCR) repertoire and TCR-dependent function. ATOs initiated with TCR-engineered HSPCs produced T cells with antigen-specific cytotoxicity and near-complete lack of endogenous TCR Vβ expression, consistent with allelic exclusion of Vβ-encoding loci. ATOs provide a robust tool for studying human T cell differentiation and for the future development of stem-cell-based engineered T cell therapies. More... »

PAGES

521-530

References to SciGraph publications

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/nmeth.4237

    DOI

    http://dx.doi.org/10.1038/nmeth.4237

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1084509216

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/28369043


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