Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro
Induction of T cell development from hematopoietic progenitor cells by delta-like-1 in vitro
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DOI：
10.1016/s1074-7613(02)00474-0
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发表时间：
2002-12-01
期刊：
影响因子：
32.4
通讯作者：
Zúñiga-Pflücker, JC
中科院分区：
文献类型：
--
作者：
Schmitt, TM;Zúñiga-Pflücker, JC
由胸腺微环境提供的预测T细胞发育的分子相互作用仍然不清楚。在这里，我们表明，异位表达的Notch配体三角洲样-1的骨髓基质细胞系失去了支持B细胞淋巴细胞生成的能力，但获得的能力，诱导造血祖细胞分化为CD 4-CD 8双阳性和单阳性T细胞。产生γ β-TCR+和γ β-TCR + T细胞，并且CD 8（+）TCR hi细胞在CD 3/TCR刺激后产生γ-干扰素。这些结果表明，在基质细胞上的Delta样-1的表达提供了诱导T细胞谱系定型、阶段特异性祖细胞扩增、TCR基因重排和T细胞分化的关键信号，在没有胸腺的情况下。因此，可能的是，胸腺的Delta-like-1/Notch相互作用支持其促进T细胞谱系定型和分化的独特能力。
The molecular interactions provided by the thymic microenvironment that predicate T cell development remain obscure. Here, we show that a bone marrow stromal cell line ectopically expressing the Notch ligand Delta-like-1 loses its ability to support B cell lymphopoiesis, but acquires the capacity to induce the differentiation of hematopoietic progenitors into CD4 CD8 double- and single-positive T cells. Both gammabeta-TCR+ and alphabeta-TCR+ T cells are generated, and CD8(+) TCRhi cells produce gamma-interferon following CD3/TCR stimulation. These results establish that expression of Delta-like-1 on stromal cells provides key signals for the induction of T cell lineage commitment, stage-specific progenitor expansion, TCR gene rearrangement, and T cell differentiation in the absence of a thymus. Thus, it is likely that Delta-like-1/Notch interactions by the thymus underpin its unique ability to promote lineage commitment and differentiation of T cells.