Thymic differentiation of TCR alpha beta(+) CD8 alpha alpha(+) IELs.
Thymic differentiation of TCR alpha beta(+) CD8 alpha alpha(+) IELs.
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DOI：
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发表时间：
2007
影响因子：
8.7
通讯作者：
F. Lambolez;M. Kronenberg;H. Cheroutre
中科院分区：
文献类型：
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作者：
F. Lambolez;M. Kronenberg;H. Cheroutre
上皮内淋巴细胞(IEL)包括几个亚群，但T细胞受体(TCR)αβ(+)CD8α(+)IEL的起源一直存在特别大的争议。在这里，我们提供了一个基于最近的工作的综述，试图统一不同的观点。肠在淋巴生成中具有原始功能，在上皮和固有层中都发现了具有分化为T细胞潜能的前体细胞。此外，据报道，胸腺将未完全分化的细胞输出到肠道。在肠道中，TCRαβ(+)CD8α(+)IEL可以从这些来源中区分出来，但在正常的胸腺小鼠中，胸腺似乎是TCRαβ(+)CD8α(+)IEL的主要来源。这种独特的IEL亚群是一种自我反应的群体，需要暴露于自我激动剂以在胸腺中进行选择，类似于其他调节性T细胞群体。IEL通过胸腺中的双阳性(DP)中间体传递，但它们起源于DP细胞的一个子集，可以通过其CD8α同源二聚体的表达来识别。胸腺中的激动剂选择的细胞是TCRbeta(+)，但CD4和CD8双阴性。有证据表明，CD8α的重新表达和CD5的下调发生在胸腺输出后，可能是在白细胞介素15的影响下在肠道中发生的。作为激动剂暴露的结果，一个新的基因表达程序被激活。因此，对TCRαβ(+)CD8α(+)IEL的发育起源的深入了解可能有助于我们理解它们如何参与肠道的免疫调节和保护。
Intraepithelial lymphocytes (IELs) contain several subsets, but the origin of the T-cell receptor (TCR)alphabeta(+) CD8 alpha alpha(+) IELs has been particularly controversial. Here we provide a synthesis, based on recent work, that attempts to unify the divergent views. The intestine has a primordial function in lymphopoiesis, and precursors with the potential to differentiate into T cells are found both in the epithelium and underlying lamina propria. Moreover, the thymus has been reported to export cells to the intestine that are not fully differentiated. TCR alpha beta(+) CD8 alpha alpha(+) IELs can differentiate in the intestine from each of these sources, but in normal euthymic mice, the thymus appears to be the major source for TCR alpha beta(+) CD8 alpha alpha(+) IELs. This unique IEL subset is a self-reactive population that requires exposure to self-agonists for selection in the thymus, similar to other regulatory T-cell populations. IELs transition through a double-positive (DP) intermediate in the thymus, but they originate from a subset of the DP cells that can be identified by its expression of CD8 alpha alpha homodimers. The agonist-selected cells in the thymus are TCRbeta(+) but CD4 and CD8 double negative. The evidence suggests that reacquired expression of CD8 alpha alpha and downregulation of CD5 occur after thymus export, perhaps in the intestine under the influence of interleukin-15. As a result of agonist exposure, a new gene expression program is activated. Therefore, the increased understanding of the developmental origin of TCR alpha beta(+) CD8 alpha alpha(+) IELs may help us to understand how they participate in immune regulation and protection in the intestine.