Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways
Ectopic expression of a T-box transcription factor, eomesodermin, renders CD4+ Th cells cytotoxic by activating both perforin- and FasL-pathways
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DOI：
10.1016/j.imlet.2012.02.013
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发表时间：
2012-05-30
影响因子：
4.4
通讯作者：
Shinohara, Nobukata
中科院分区：
文献类型：
--
作者：
Eshima, Koji;Chiba, Sayuri;Shinohara, Nobukata
病毒感染期间。 CD8+细胞毒性T淋巴细胞（CTL）通过利用穿孔素/颗粒酶途径和FasL-Fas途径这两种溶细胞途径破坏病毒感染的细胞，在消除病毒方面发挥着核心作用。研究表明，CTL 的效应功能受到两种 T-box 转录因子 T-bet 和 eomesodermin (Eomes) 的关键控制，尽管它们在构建 CTL 功能中的精确活性尚未完全了解。为了研究Eomes的功能效力和活性，分析了两个终末分化的鼠CD4(+)Th细胞系中Eomes的异位表达对其效应子功能的影响。结果显示，在Eomes转染的Th杂交瘤中，Con A刺激后细胞表面FasL表达显着增强，但穿孔素表达并未被诱导。在正常的、未转化的 Th2 细胞中，Eomes 的引入引发了穿孔素的表达，并且还增强了 FasL 的上调。有趣的是，Eomes转染子的溶细胞活性比穿孔素转染的Th2细胞更有效，后者表达高水平的穿孔素和颗粒酶B mRNA，这表明Eomes除了制备这些溶细胞效应分子之外还可能发挥其他作用。相反，刺激诱导的 CD154 上调（典型的辅助 T 细胞特征之一）在 Eomes 转染子中受到抑制。总的来说，这些结果表明 Eomes 可能不仅参与穿孔素/颗粒酶的表达，而且还发挥各种功能，包括 FasL 上调，以形成 CD8(+) CTL 的特征。这些研究还表明，单独引入 Eomes 足以将完全分化的 Th 细胞的功能转变为 CTL 的功能 (C) 2012 Elsevier B.V. 保留所有权利。
During viral infection. CD8(+) cytotoxic T lymphocytes (CTL) play a central role to eliminate viruses by destructing virus-infected cells utilizing two cytolytic pathways, i.e., perforin/granzyme pathway and FasL-Fas pathway. It has been shown that effector functions of CTL are critically controlled by two T-box transcription factors, T-bet and eomesodermin (Eomes), although their precise activities in constructing CTL functions are not fully understood. To investigate the functional potency and activities of Eomes, the effects of ectopic expression of Eomes in two terminally differentiated murine CD4(+) Th lines, on their effector functions were analyzed. The results showed that in Eomes-transfected Th hybridoma, cell surface FasL expression upon Con A stimulation was markedly enhanced, although perforin expression was not induced. In normal, non-transformed Th2 cells, introduction of Eomes elicited perforin expression, and also augmented FasL up-regulation. Interestingly, cyotlytic activity of Eomes-transfectant was more efficient than that of perforin-transfected Th2 cells which expressed high levels of perforin and granzyme B mRNA, indicating that Eomes may play additional roles other than preparation of these cytolytic effector molecules. In contrast, stimulation-induced CD154 up-regulation, one of the typical helper T cell characteristics, was repressed in Eomes-transfectant. Collectively, these results suggest that Eomes may not only be involved in perforin/granzyme expression but also play various functions, including FasL up-regulation, to develop the characteristics of CD8(+) CTL These studies have also suggested that introduction of Eomes alone was sufficient to convert the functions of fully differentiated Th cells toward those of CTL (C) 2012 Elsevier B.V. All rights reserved.