Messi Mara, Giacchetto Isabella, Nagata Kinya, Lanzavecchia Antonio, Natoli Gioacchino, Sallusto Federica
Institute for Research in Biomedicine, Via Vincenzo Vela 6, CH-6500 Bellinzona, Switzerland.
Nat Immunol. 2003 Jan;4(1):78-86. doi: 10.1038/ni872. Epub 2002 Nov 25.
CD4+ T cell priming under T helper type I (T(H)1) or T(H)2 conditions gives rise to polarized cytokine gene expression. We found that in these conditions human naive T cells acquired stable histone hyperacetylation at either the Ifng or Il4 promoter. Effector memory T cells showed polarized cytokine gene acetylation patterns in vivo, whereas central memory T cells had hypoacetylated cytokine genes but acquired polarized acetylation and expression after appropriate stimulation. However, hypoacetylation of the nonexpressed cytokine gene did not lead to irreversible silencing because most T(H)1 and T(H)2 cells acetylated and expressed the alternative gene when stimulated under opposite T(H) conditions. Such cytokine flexibility was absent in a subset of T(H)2 cells that failed to up-regulate T-bet and to express interferon-gamma when stimulated under T(H)1 conditions. Thus, most human CD4+ T cells retain both memory and flexibility of cytokine gene expression.
在I型辅助性T细胞（T(H)1）或T(H)2条件下的CD4+ T细胞启动会导致细胞因子基因表达极化。我们发现，在这些条件下，人类初始T细胞在Ifng或Il4启动子处获得稳定的组蛋白高度乙酰化。效应记忆T细胞在体内表现出极化的细胞因子基因乙酰化模式，而中枢记忆T细胞的细胞因子基因乙酰化程度较低，但在适当刺激后会获得极化的乙酰化和表达。然而，未表达的细胞因子基因的低乙酰化并不会导致不可逆的沉默，因为大多数T(H)1和T(H)2细胞在相反的T(H)条件下受到刺激时会乙酰化并表达另一种基因。在一部分T(H)2细胞中不存在这种细胞因子灵活性，这些细胞在T(H)1条件下受到刺激时无法上调T-bet并表达干扰素-γ。因此，大多数人类CD4+ T细胞保留了细胞因子基因表达的记忆和灵活性。
