Plum J, De Smedt M, Defresne M P, Leclercq G, Vandekerckhove B
Department of Clinical Chemistry, Microbiology and Immunology, University of Ghent, University Hospital, Belgium.
Blood. 1994 Sep 1;84(5):1587-93.
Hematopoietic stem cells differentiate in the thymus to T cells along precisely defined intermediates. This process is thymic epithelium dependent and involves cytokines and cell-cell interactions between thymic stroma and T-cell precursors. Here we report that highly purified human CD34++ fetal liver stem cells differentiate to mature T cells, when seeded into isolated fetal thymic lobes of severe combined immunodeficient mice, and subsequently cultured in vitro. The human stem cells differentiate sequentially into CD4+CD8-CD3-, CD4+CD8+CD3-, CD4+CD8+CD3+, and finally, CD4+CD8-CD3+4 and CD4-CD8+CD3++ cells. Phenotypic analysis for additional maturation markers showed that these CD4 and CD8 single-positive thymocytes are fully maturate cells. By immunochemistry, human HLA-DR+ cells with a dendritic morphology could be detected. This novel chimeric human-mouse fetal thymus organ culture offers a tool to study human T-cell ontogeny in vitro and is a rapid and reliable test method for T-cell precursor activity of cultured or transfected human stem cells.
造血干细胞在胸腺中沿着精确界定的中间阶段分化为T细胞。这一过程依赖胸腺上皮，涉及细胞因子以及胸腺基质与T细胞前体之间的细胞间相互作用。我们在此报告，当将高度纯化的人CD34++胎儿肝脏干细胞接种到重症联合免疫缺陷小鼠的分离胎儿胸腺叶中，随后进行体外培养时，它们会分化为成熟T细胞。人干细胞依次分化为CD4+CD8-CD3-、CD4+CD8+CD3-、CD4+CD8+CD3+，最终分化为CD4+CD8-CD3+4和CD4-CD8+CD3++细胞。对其他成熟标志物的表型分析表明，这些CD4和CD8单阳性胸腺细胞是完全成熟的细胞。通过免疫化学方法，可检测到具有树突状形态的人HLA-DR+细胞。这种新型的人-鼠嵌合胎儿胸腺器官培养为体外研究人T细胞个体发生提供了一种工具，并且是一种用于检测培养或转染的人干细胞T细胞前体活性的快速可靠的测试方法。
