IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes
IL-10 is excluded from the functional cytokine memory of human CD4+ memory T lymphocytes
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DOI：
10.4049/jimmunol.179.4.2389
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发表时间：
2007-08-15
影响因子：
4.4
通讯作者：
Thiel, Andreas
中科院分区：
文献类型：
--
作者：
Dong, Jun;Ivascu, Claudia;Thiel, Andreas
表观遗传修饰，包括DNA甲基化，深刻影响CD4(+)Th特异性细胞的基因表达，从而塑造记忆Th细胞功能。我们在这里证明了人类记忆Th细胞缺乏重新表达免疫调节细胞因子基因IL10的固定潜力与其DNA甲基化状态之间的相关性。从健康志愿者外周血中直接分离出分泌IL-10或干扰素-γ的记忆Th细胞，检测IL-10和IFNG的DNA甲基化状态。与不分泌IL-10的Th细胞或从体外建立的人Th1和Th2克隆相比，分泌IL-10的Th细胞中IL-10基因的甲基化差异有限。相反，在干扰素-(γ+)记忆Th细胞中，与不分泌干扰素-γ的记忆Th细胞相比，IFNG基因的启动子低甲基化。与缺乏表观遗传记忆相一致，几乎90%的体外分离的分泌IL-10的Th细胞在重新刺激后缺乏重新表达IL-10的功能记忆。我们的数据表明，与IFNG等效应细胞因子基因不同，IL10在人类记忆Th细胞中没有表观遗传标记。从体外人类CD4(+)T淋巴细胞的功能记忆中排除IL-10，而不是效应性细胞因子，可能反映了由于其强大的免疫调节潜力，需要适当地调节IL-10的分泌。
Epigenetic modifications, including DNA methylation, profoundly influence gene expression of CD4(+) Th-specific cells thereby shaping memory Th cell function. We demonstrate here a correlation between a lacking fixed potential of human memory Th cells to re-express the immunoregulatory cytokine gene IL10 and its DNA methylation status. Memory Th cells secreting IL-10 or IFN-gamma were directly isolated ex vivo from peripheral blood of healthy volunteers, and the DNA methylation status of IL10 and IFNG was assessed. Limited difference in methylation was found for the IL10 gene locus in IL-10-secreting Th cells, as compared with Th cells not secreting IL-10 isolated directly ex vivo or from in vitro-established human Th1 and Th2 clones. In contrast, in IFN-(gamma+) memory Th cells the promoter of the IFNG gene was hypomethylated, as compared with IFN-gamma-nonsecreting memory Th cells. In accordance with the lack of epigenetic memory, almost 90% of ex vivo-isolated IL-10-secreting Th cells lacked a functional memory for IL-10 re-expression after restimulation. Our data indicate that IL10 does not become epigenetically marked in human memory Th cells unlike effector cytokine genes such as IFNG. The exclusion of IL-10, but not effector cytokines, from the functional memory of human CD4(+) T lymphocytes ex vivo may reflect the need for appropriate regulation of IL-10 secretion, due to its potent immunoregulatory potential.