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小鼠胸腺T细胞发育过程中的c-kit+成熟途径:谱系与选择

The c-kit+ maturation pathway in mouse thymic T cell development: lineages and selection.

作者信息

Akashi K, Weissman I L

机构信息

Department of Pathology, Stanford University School of Medicine, California 94305, USA.

出版信息

Immunity. 1996 Aug;5(2):147-61. doi: 10.1016/s1074-7613(00)80491-4.

DOI:10.1016/s1074-7613(00)80491-4
PMID:8769478
Abstract

Positive selection of T cells begins with TCR alpha beta lo thymic progenitors. Here, we show that the most efficient TCRlo progenitors are c-kit+ with intermediate levels of CD4 and CD8 (DPint). Positive selection of DPint TCRlo c-kit+ cells results in TCRmed CD69+ c-kit+ transitional intermediates that show increased TCRV beta frequencies to selecting superantigen (SAg) that are committed to the CD4 or CD8 pathway. The cells on the c-kit+ maturation pathway maintain Bcl-2 expression. Most DPint c-kit+ progenitors fail positive selection, and become DPhi c-kit- cells that lose Bcl-2 expression. Some DPhi c-kit blast cells can be salvaged to produce mature single-positive (SP) cells. DPint c-kit+ maturation to SP cells can occur in <12 hr in vitro on thymic stromal monolayers.

摘要

T细胞的阳性选择始于TCRαβ低表达的胸腺祖细胞。在此,我们表明最有效的TCR低表达祖细胞是c-kit阳性且CD4和CD8处于中等水平(双阳性中间型,DPint)的细胞。DPint TCR低表达c-kit阳性细胞的阳性选择产生TCR中等水平CD69阳性c-kit阳性的过渡性中间细胞,这些细胞针对选择超抗原(SAg)的TCRVβ频率增加,且已定向至CD4或CD8途径。处于c-kit阳性成熟途径的细胞维持Bcl-2表达。大多数DPint c-kit阳性祖细胞未能通过阳性选择,成为失去Bcl-2表达的双阴性c-kit阴性细胞。一些双阴性c-kit母细胞可被挽救以产生成熟的单阳性(SP)细胞。DPint c-kit阳性细胞在体外胸腺基质单层上可在不到12小时内成熟为SP细胞。

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