Cytokine-dependent blimp-1 expression in activated T cells inhibits IL-2 production
Cytokine-dependent blimp-1 expression in activated T cells inhibits IL-2 production
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DOI：
10.4049/jimmunol.178.1.242
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发表时间：
2007-01-01
影响因子：
4.4
通讯作者：
Malek, Thomas R.
中科院分区：
文献类型：
--
作者：
Gong, Dapeng;Malek, Thomas R.
在体外初始T细胞的Ag活化后，广泛的生长和分化成效应细胞依赖于IL-2。DNA微阵列分析用于鉴定调节该过程的IL-2依赖性分子。在这项研究中，我们表明，转录抑制因子B淋巴细胞诱导的成熟蛋白1（Blimp-1）的表达由一个依赖于嘌呤的途径在活化的T淋巴细胞。活化的CD 4（+）和CD 8（+）T细胞产生的IL-2与Blimp-1水平呈负相关，因为较高的IL-2产生与较低的Blimp-1表达相关。此外，激活的T细胞异位表达Blimp-1抑制IL-2的产生，但增强颗粒酶B和CD 25的表达。总的来说，这些发现表明在活化的T细胞中存在负反馈调节环，使得IL-2通过诱导Blimp-1抑制其自身的产生，同时促进效应细胞表型。
After Ag activation of naive T cells in vitro, extensive growth and differentiation into effector cells depend upon IL-2. DNA microarray analysis was used to identify IL-2-dependent molecules regulating this process. In this study, we show that the transcriptional repressor B lymphocyte-induced maturation protein 1 (Blimp-1) is expressed by a cytokine-dependent pathway in activated T lymphocytes. IL-2 production by activated CD4(+) and CD8(+) T cells inversely correlated with Blimp-1 levels as higher IL-2 production was associated with lower Blimp-1 expression. Furthermore, ectopic expression of Blimp-1 by activated T cells inhibited IL-2 production but enhanced granzyme B and CD25 expression. Collectively, these findings indicate that there is a negative feedback regulatory loop in activated T cells such that IL-2 inhibits its own production through induction of Blimp-1 while promoting an effector cell phenotype.