Propensity of adult lymphoid progenitors to progress to DN2/3 stage thymocytes with Notch receptor ligation
Propensity of adult lymphoid progenitors to progress to DN2/3 stage thymocytes with Notch receptor ligation
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DOI：
10.4049/jimmunol.175.8.4858
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发表时间：
2005-10-15
影响因子：
4.4
通讯作者：
Kincade, PW
中科院分区：
文献类型：
--
作者：
Huang, JX;Garrett, KP;Kincade, PW
Notch家族受体控制免疫系统中特化细胞的产生和补充中的关键事件。然而，目前还不清楚Notch信号是否调节同质祖细胞中突然的二元谱系选择，或者对该过程的多个方面具有更渐进的影响。最近开发的与Delta 1转导的基质细胞的共培养系统被广泛用于解决这些基本问题。与胎儿祖细胞不同，多种类型的成人骨髓细胞在鼠Delta样1转导的OP 9细胞共培养物中无限扩增，进展到DN 2/DN 3胸腺细胞阶段，并缓慢产生TCR+和NK细胞。这种细胞长期培养后仍具有体内T淋巴细胞生成的潜能。成人骨髓进展通过双阳性和单阳性阶段，只有当IL-7浓度低，通道很少。Lin（-）c-Kit（低）GFP（+）IL-7 R α（+/-）前淋巴细胞是短期培养中最有效的成人骨髓细胞，但该试验不一定反映通常负责补充成人胸腺的细胞。尽管在该模型中，具有IG D-H-J（H）重排产物的骨髓来源的祖细胞获得了T谱系特征，但具有更多V-H-D（H）J（H）重排产物的B定型细胞并非如此。
Notch family. receptors control critical events in the production and replenishment of specialized cells in the immune system. However, it is unclear whether Notch signaling regulates abrupt binary lineage choices in homogeneous progenitors or has more gradual influence over multiple aspects of the process. A recently developed coculture system with Delta 1-transduced stromal cells is being extensively used to address such fundamental questions. Different from fetal progenitors, multiple types of adult marrow cells expanded indefinitely in murine Delta-like 1-transduced OP9 cell cocultures, progressed to a DN2/DN3 thymocyte stage, and slowly produced TCR+ and NK cells. Long-term cultured cells of this kind retained so I me potential for T lymphopoiesis in vivo. Adult marrow progressed through double-positive and single-positive stages only when IL-7 concentrations were low and passages were infrequent. Lin(-)c-Kit(low)GFP(+)IL-7R alpha(+/-) prolymphocytes were the most efficient of adult bone marrow cells in short-term cultures, but the assay does not necessarily reflect cells normally responsible for replenishing the adult thymus. Although marrow-derived progenitors with Ig D-H-J(H) rearrangements acquired T lineage characteristics in this model, that was not the case for more B committed cells with V-H-D(H)J(H) rearrangement products.