Developmental and molecular characterization of emerging β- and γδ-selected pre-T cells in the adult mouse thymus
Developmental and molecular characterization of emerging β- and γδ-selected pre-T cells in the adult mouse thymus
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DOI：
10.1016/j.immuni.2005.11.012
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发表时间：
2006-01-01
期刊：
影响因子：
32.4
通讯作者：
Rothenberg, EV
中科院分区：
文献类型：
--
作者：
Taghon, T;Yui, MA;Rothenberg, EV
T细胞发育中的第一个检查点，β选择，由于缺乏特异性表面标志物而尚未完全表征。我们发现，CD 27在启动β选择的DN 3胸腺细胞中上调，伴随着细胞内TCR-β表达。克隆分析确定，CD 27高DN 3细胞以超过90%的效率产生CD 4（+）CD 8（+）子代，比CD 27（低）大多数更快和更有效。在TCR-β（-/-）小鼠和IL 2-GFP转基因报告小鼠中，CD 27上调也发生在γ δ选择的DN 3胸腺细胞中，其中GFP标记来自DN 3胸腺细胞的最早出现的TCR-γ δ细胞。用CD 27来区分选择前和选择后的DN 3细胞，详细的基因表达分析定义了与检查点阻滞、β选择和γ δ选择相关的调控变化。与β选择相比，γ δ选择诱导更高的CD 5、Egr和Runx 3表达，但其触发较少的增殖。我们的研究结果还揭示了Notch/Delta依赖性在发展中的α β和γ δ T谱系细胞之间的分歧的最早阶段的差异。
The first checkpoint in T cell development, beta selection, has remained incompletely characterized for lack of specific surface markers. We show that CD27 is upregulated in DN3 thymocytes initiating beta selection, concomitant with intracellular TCR-beta expression. Clonal analysis determined that CD27 high DN3 cells generate CD4(+)CD8(+) progeny with more than 90% efficiency, faster and more efficiently than the CD27(low) majority. CD27 upregulation also occurs in gamma delta-selected DN3 thymocytes in TCR-beta(-/-) mice and in IL2-GFP transgenic reporter mice where GFP marks the earliest emerging TCR-gamma delta cells from DN3 thymocytes. With CD27 to distinguish pre- and postselection DN3 cells, a detailed gene expression analysis defined regulatory changes associated with checkpoint arrest, with beta selection, and with gamma delta selection. gamma delta selection induces higher CD5, Egr, and Runx3 expression as compared to beta selection, but it triggers less proliferation. Our results also reveal differences in Notch/Delta dependence at the earliest stages of divergence between developing alpha beta and gamma delta T-lineage cells.