Generation of mature T cells from human hematopoietic stem and progenitor cells in artificial thymic organoids.

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 cel

SUBMITTER: Seet CS 

PROVIDER: S-EPMC5426913 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature