Regulation of cell death and survival in intestinal intraepithelial lymphocytes
Regulation of cell death and survival in intestinal intraepithelial lymphocytes
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DOI：
10.1038/sj.cdd.4400854
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发表时间：
2001-07-01
影响因子：
12.4
通讯作者：
Frutschi, C
中科院分区：
文献类型：
--
作者：
Brunner, T;Arnold, D;Frutschi, C
小鼠小肠的上皮内淋巴细胞（IEL）是一群独特的细胞，主要是CD8(+) T淋巴细胞，位于肠黏膜的上皮细胞层内。与上皮细胞的紧密相互作用似乎对IEL的存活至关重要，因为分离和体外培养会导致这群淋巴细胞大量凋亡。在此，我们提供的证据表明，这种IEL细胞死亡形式可能至少部分由内源性产生的糖皮质激素介导，因为肾上腺切除或用糖皮质激素受体拮抗剂处理小鼠显著提高了IEL的体外存活率。我们进一步证明，IEL的体外激活诱导抗凋亡基因产物的上调，弥补了存活细胞因子的缺乏，并从凋亡细胞死亡中挽救回来。因此，与胸腺细胞和T细胞杂交瘤类似，IEL的存活可能受TCR激活和糖皮质激素的拮抗作用调节。
Intraepithelial lymphocytes (IEL) of the small murine bower represent a unique population of mostly CD8(+) T lymphocytes that reside within the epithelial cell layer of the intestinal mucosa. The close interaction with epithelial cells appears to be crucial for IEL survival since isolation and ex vivo culture induces massive apoptosis in this lymphocyte population. Here, we provide evidence that this form of IEL cell death may be mediated at least in part by endogenously produced glucocorticoids since adrenalectomy or treatment of mice with a glucocorticoid receptor antagonist significantly enhanced ex vivo survival of IEL, We further demonstrate that ex vivo activation of IEL induces upregulation of anti-apoptotic gene products, compensates for the lack of survival cytokines and rescues from apoptotic cell death, Thus, similar to thymocytes and T cell hybridomas, IEL survival may be regulated by the antagonistic action of TCR activation and glucocorticoids.