Cutting Edge: Transcription Factor BCL6 Is Required for the Generation, but Not Maintenance, of Memory CD8+ T Cells in Acute Viral Infection
Cutting Edge: Transcription Factor BCL6 Is Required for the Generation, but Not Maintenance, of Memory CD8+ T Cells in Acute Viral Infection
复制标题
尖端技术：急性病毒感染中记忆 CD8( ) T 细胞的生成而非维持需要转录因子 BCL6
DOI：
10.4049/jimmunol.1900014
复制
发表时间：
2019-07-15
影响因子：
4.4
通讯作者：
Zhou, Xinyuan
中科院分区：
文献类型：
--
作者：
Liu, Zhenyu;Guo, Yanyan;Zhou, Xinyuan
要点 BCL6 对于记忆 CD8+ T 细胞的维持是不可或缺的。 BCL6 是 CD8+ 记忆前体的生成所必需的。 BCL6 促进 CD8+ 记忆前体细胞中 TCF-1 的表达。记忆 CD8+ T 细胞的分化对于长期细胞免疫至关重要。据报道，转录因子 BCL6 对于记忆 CD8+ T 细胞的生成和维持非常重要。然而，使用新建立的BCL6条件敲除小鼠模型，我们证明BCL6对于维持已建立的记忆CD8+T细胞库是可有可无的，尽管在急性病毒感染时BCL6仍然是CD8+记忆前体的生成所必需的。此外，BCL6通过直接结合CD8+记忆前体中的Tcf7（TCF-1的基因符号）等位基因来促进TCF-1的表达，并且TCF-1的强制表达恢复了BCL6缺陷的记忆前体的生成。因此，我们的研究结果阐明，BCL6 对于记忆 CD8+ T 细胞的维持是可有可无的，但在急性病毒感染中作为 TCF-1 的重要上游调节记忆前体的生成。
Key Points BCL6 is dispensable for the maintenance of memory CD8+ T cells. BCL6 is required for the generation of CD8+ memory precursors. BCL6 promotes TCF-1 expression in CD8+ memory precursors. The differentiation of memory CD8+ T cells is critical to the long-term cellular immunity. The transcription factor BCL6 has been reportedly important for the generation and maintenance of memory CD8+ T cells; however, using the newly established BCL6 conditional knockout mouse model, we demonstrate that BCL6 is dispensable for the maintenance of established memory CD8+ T cell pool, although BCL6 is still required for the generation of CD8+ memory precursors upon acute viral infection. In addition, BCL6 promotes the expression of TCF-1 via directly binding to the Tcf7 (gene symbol for TCF-1) allele in CD8+ memory precursors and forced expression of TCF-1 restores the generation of BCL6-deficient memory precursors. Thus, our findings clarify that BCL6 is dispensable for the maintenance of memory CD8+ T cells, but functions as an important upstream of TCF-1 to regulate the generation of memory precursors in acute viral infection.