When dormant naïve T cells first become activated by antigen‐presenting cells, they express the autocrine growth factor IL‐2 which transforms them into rapidly dividing effector T cells. During this process, hundreds of genes undergo epigenetic reprogramming for efficient activation, and also for potential reactivation after they return to quiescence as memory T cells. However, the relative contributions of IL‐2 and T cell receptor signaling to this process are unknown. Here, we show that IL‐2 signaling is required to maintain open chromatin at hundreds of gene regulatory elements, many of which control subsequent stimulus‐dependent alternative pathways of T cell differentiation. We demonstrate that IL‐2 activates binding of AP‐1 and STAT5 at sites that can subsequently bind lineage‐determining transcription factors, depending upon what other external factors exist in the local T cell environment. Once established, priming can also be maintained by the stroma‐derived homeostatic cytokine IL‐7, and priming diminishes if Il7r is subsequently deleted in vivo. Hence, IL‐2 is not just a growth factor; it lays the foundation for T cell differentiation and immunological memory.

中文翻译：

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IL-2/IL-7 诱导因子在谱系定义因子之前开辟了 T 细胞分化的途径。

当休眠的初始 T 细胞首次被抗原呈递细胞激活时，它们会表达自分泌生长因子 IL-2，从而将它们转化为快速分裂的效应 T 细胞。在此过程中，数百个基因经历表观遗传重编程以有效激活，并在它们作为记忆 T 细胞返回静止状态后进行潜在的重新激活。然而，IL-2 和 T 细胞受体信号传导对该过程的相对贡献尚不清楚。在这里，我们表明需要 IL-2 信号来维持数百个基因调控元件的开放染色质，其中许多控制随后的刺激依赖性 T 细胞分化的替代途径。我们证明 IL-2 在随后可以结合谱系决定转录因子的位点激活 AP-1 和 STAT5 的结合，取决于本地 T 细胞环境中存在哪些其他外部因素。一旦建立，启动也可以由基质衍生的稳态细胞因子 IL-7 维持，如果启动会减弱Il7r随后在体内被删除。因此，IL-2 不仅仅是一种生长因子；它为T细胞分化和免疫记忆奠定了基础。