Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant
Selection of the cutaneous intraepithelial γδ+ T cell repertoire by a thymic stromal determinant
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DOI：
10.1038/ni1363
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发表时间：
2006-08-01
影响因子：
30.5
通讯作者：
Tigelaar, Robert E.
中科院分区：
文献类型：
--
作者：
Lewis, Julia M.;Girardi, Michael;Tigelaar, Robert E.
上皮内淋巴细胞是一组主要表达单特异性或寡克隆T细胞受体(TCR)的T细胞。与适应性TCRαβ(+)T细胞一样，上皮内淋巴细胞是胸腺表达的自身激动剂对TCRγβ(+)T细胞的阳性选择，但目前尚无直接证据表明这一点。小鼠树突状表皮T细胞是典型的上皮内淋巴细胞，表现为几乎单克隆性的TCRγ-增量(+)谱系。在这里，我们描述了一种FVB亚系的小鼠，在这种亚系中，这种谱系被独特地耗尽，导致皮肤病理。这种表型是由于树突状表皮T细胞前体细胞未能成熟，这是因为胸腺基质使用的一个显性基因存在可遗传缺陷，该基因用于‘教育’自然的、皮肤相关的上皮内淋巴细胞库，使其具有生理用途。
Intraepithelial lymphocytes constitute a group of T cells that express mainly monospecific or oligoclonal T cell receptors (TCRs). Like adaptive TCR alpha beta(+) T cells, intraepithelial lymphocytes, a subset enriched in TCR gamma delta(+) T cells, are proposed to be positively selected by thymically expressed self agonists, yet no direct evidence for this exists at present. Mouse dendritic epidermal T cells are prototypic intraepithelial lymphocytes, displaying an almost monoclonal TCR gamma delta(+) repertoire. Here we describe an FVB substrain of mice in which this repertoire was uniquely depleted, resulting in cutaneous pathology. This phenotype was due to failure of dendritic epidermal T cell progenitors to mature because of a heritable defect in a dominant gene used by the thymic stroma to 'educate' the natural, skin- associated intraepithelial lymphocyte repertoire to be of physiological use.