Two distinct pathways of positive selection for thymocytes
Two distinct pathways of positive selection for thymocytes
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DOI：
10.1073/pnas.95.5.2486
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发表时间：
1998-03-03
影响因子：
11.1
通讯作者：
Weissman, IL
中科院分区：
文献类型：
--
作者：
Akashi, K;Kondo, M;Weissman, IL
大多数小鼠胸腺细胞经历正选择被发现在两个途径之一; c-Kit（+）和c-Kit（-）途径。在这里，我们表明，c-Kit和白细胞介素-7受体（IL-7 R）介导的信号支持从首先表达细胞表面T细胞受体（TCR）的亚群-TCR α/β（lo）CD 4（int）/CD 8（int）（DPint）c-Kit（+）细胞向TCR α/β（med）c-Kit（+）过渡中间细胞（c-Kit（+）途径）过渡期间的正选择。在c-Kit（+）途径上未通过阳性选择的细胞成为TCR α/β（lo）c-Kit（-）（DPhi）原始细胞，其似乎经历替代性TCR α重排。因此，通过表达自身主要组织相容性复合物可选择的TCR α/β而挽救用于阳性选择的罕见DP（hi）c-Kit（-）母细胞上调IL-7 R，但不上调c-Kit，并且是c-Kit（-）途径上的主要祖细胞;该c-Kit（-）IL-7 R（+）途径主要是CD 4谱系定型的。细胞分裂是TCR（lo.med）c-Kit（+）转变的特征，但对于DP（hi）c-Kit（-）母细胞的CD 4谱系成熟并非必需。在这种观点中，c-Kit（-）路径上的阳性选择是由c-Kit（+）路径上的阳性选择失败的细胞的补救引起的。
Most mouse thymocytes undergoing positive selection are found on one of two pathways; the c-Kit(+) and the c-Kit(-) pathways. Here, we show that c-Kit and interleukin-7 receptor (IL-7R)-mediated signals support positive selection during the transition from the subpopulation that first expresses cell surface T cell receptor (TCR)--the TCR alpha/beta(lo)CD4(int)/CD8(int) (DPint) c-Kit(+) cells to TCR alpha/beta(med)c-Kit(+) transitional intermediate cells (the c-Kit(+) pathway). Cells that fail positive selection on the c-Kit(+) pathway become TCR alpha/beta(lo)c-Kit(-) (DPhi) blasts that appear to undergo alternative TCR alpha rearrangements. The rare DP(hi)c-Kit(-) blast cells that thus are salvaged for positive selection by expressing a self-major histocompatibility complex selectable TCR alpha/beta upregulate IL-7R, but not c-Kit, and are the principal progenitors on the c-Kit(-) pathway; this c-Kit(-)IL-7R(+) pathway is mainly CD4 lineage committed. Cell division is a feature of the TCR(lo.med)c-Kit(+) transition, but is not essential for CD4 lineage maturation from DP(hi)c-Kit(-) blasts. In this view, positive selection on the c-Kit(-) path results from a salvage of cells that failed positive selection on the c-Kit(+) path.