Cutting edge: Chromatin remodeling as a molecular basis for the enhanced functionality of memory CD8 T cells
Cutting edge: Chromatin remodeling as a molecular basis for the enhanced functionality of memory CD8 T cells
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DOI：
10.4049/jimmunol.181.2.865
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发表时间：
2008-07-15
影响因子：
4.4
通讯作者：
Shen, Hao
中科院分区：
文献类型：
--
作者：
Northrop, John K.;Wells, Andrew D.;Shen, Hao
记忆性CD 8 T细胞与其幼稚前体不同，能够快速产生高水平的细胞因子，杀死靶细胞，并在遇到Ag后立即增殖成许多次级效应物。这种随时准备应答的状态有助于它们赋予保护性免疫的上级能力，但其潜在的分子基础仍然未知。在这项研究中，我们发现记忆性CD 8 T细胞与幼稚CD 8 T细胞相比具有增加的组蛋白乙酰化;然而，那些在没有CD 4 T细胞帮助下激活的细胞（“未帮助”）仍然处于低乙酰化状态，并且未能发展成功能性的保护性记忆。在活化过程中用组蛋白脱乙酰酶抑制剂处理导致未带化的CD 8 T细胞中组蛋白乙酰化增加，并恢复其分化为能够立即产生细胞因子并提供保护性免疫的功能性记忆细胞的能力。这些结果表明，CD 4 T辅助依赖性染色质重塑为记忆性CD 8 T细胞增强的反应性提供了分子基础。
Memory CD8 T cells, unlike their naive precursors, are capable of rapidly producing high levels of cytokines, killing target cells, and proliferating into numerous secondary effectors immediately upon Ag encounter. This ready-to-respond state contributes to their superior ability to confer protective immunity, yet the underlying molecular basis remains unknown. In this study, we show that memory CD8 T cells have increased histone acetylation compared with naive CD8 T cells; however, those activated without CD4 T cell help ("unhelped") remain hypoacetylated and fail to develop into functional, protective memory. Treatment with a histone deacetylase inhibitor during activation results in increased histone acetylation in unbelped CD8 T cells and restores their ability to differentiate into functional memory cells capable of immediate cytokine production and providing protective immunity. These results demonstrate that CD4 T help-dependent chromatin remodeling provides a molecular basis for the enhanced responsiveness of memory CD8 T cells.