Bcl6 controls granzyme B expression in effector CD8+ T cells
Bcl6 controls granzyme B expression in effector CD8+ T cells
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DOI：
10.1002/eji.200636165
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发表时间：
2006-12-01
影响因子：
5.4
通讯作者：
Tokuhisa, Takeshi
中科院分区：
文献类型：
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作者：
Yoshida, Kazuki;Sakamoto, Akemi;Tokuhisa, Takeshi
Bcl 6是一种序列特异性转录抑制因子，对记忆性CD8（+）T细胞的产生和维持非常重要。虽然记忆性CD8（+）T细胞是由效应性CD8（+）T细胞产生的，但Bcl 6在效应性CD8（+）T细胞中的作用在很大程度上是未知的。我们发现Bcl 6的表达在活化的CD8（+）T细胞中被瞬时诱导，在效应CD8（+）T细胞中被持续上调。效应分子中颗粒酶B mRNA的量与效应分子中Bcl 6 mRNA的量呈负相关。Bcl 6在CD8（+）T细胞中的过表达导致其效应期的较低杀伤活性，支持Bcl 6降低效应CD8（+）T细胞中的颗粒酶B表达。我们确定了一个假定的Bcl 6结合的DNA序列的颗粒酶B基因的启动子区。通过染色质免疫沉淀试验，在初始CD8（+）T细胞中检测到Bcl 6与Bcl 6结合序列的结合，但在活化的CD8（+）T细胞中未检测到。此外，Bcl 6结合序列是Bcl 6抑制由颗粒酶B启动子控制的荧光素酶报告基因表达所必需的。因此，颗粒酶B基因是效应CD 8（+）T细胞中Bcl 6的分子靶点。
Bcl6, a sequence-specific transcriptional repressor, is important for generation and maintenance of memory CD8(+) T cells. Although memory CD8(+) T cells are generated from effector CD8(+) T cells, a role for Bcl6 in effector CD8(+) T cells is largely unknown. We show here that Bcl6 expression was transiently induced in activated CD8(+) T cells and continuously up-regulated in effector CD8(+) T cells. The amount of granzyme B mRNA among effector molecules produced by effector CD8(+) T cells inversely correlated with the amount of Bcl6 mRNA in CD8(+) T cells. Overexpression of Bcl6 in CD8(+) T cells resulted in lower killing activity at their effector phase, supporting the reduction of granzyme B expression in effector CD8(+) T cells by Bcl6. We identified a putative Bcl6-binding DNA sequence in the promoter region of the granzyme B gene. Binding of Bcl6 to the Bcl6-binding sequence was detected in naive CD8(+) T cells but not in activated CD8(+) T cells by chromatin immunoprecipitation assay. Furthermore, the Bcl6-binding sequence was required for Bcl6 to repress the luciferase reporter gene expression controlled by the granzyme B promoter. Thus, the granzyme B gene is a molecular target of Bcl6 in effector CD8(+) T cells.