Reactive oxygen species (ROS) increase in activated T cells because of metabolic activity induced to support T cell proliferation and differentiation. We show that these ROS trigger an oxidative stress response that leads to translation repression. This response is countered by Schlafen 2 (SLFN2), which directly binds transfer RNAs (tRNAs) to protect them from cleavage by the ribonuclease angiogenin. T cell–specific SLFN2 deficiency results in the accumulation of tRNA fragments, which inhibit translation and promote stress-granule formation. Interleukin-2 receptor β (IL-2Rβ) and IL-2Rγ fail to be translationally up-regulated after T cell receptor stimulation, rendering SLFN2-deficient T cells insensitive to interleukin-2’s mitogenic effects. SLFN2 confers resistance against the ROS-mediated translation-inhibitory effects of oxidative stress normally induced by T cell activation, permitting the robust protein synthesis necessary for T cell expansion and immunity.

由于诱导支持 T 细胞增殖和分化的代谢活动，活化 T 细胞中的活性氧 (ROS) 增加。我们表明这些 ROS 触发了导致翻译抑制的氧化应激反应。这种反应被 Schlafen 2 (SLFN2) 抵消，它直接结合转移 RNA (tRNA) 以保护它们免受核糖核酸酶血管生成素的切割。T 细胞特异性 SLFN2 缺陷导致 tRNA 片段的积累，从而抑制翻译并促进应激颗粒形成。白介素 2 受体 β (IL-2Rβ) 和 IL-2Rγ 在 T 细胞受体刺激后不能被翻译上调，导致 SLFN2 缺陷型 T 细胞对白介素 2 的促有丝分裂作用不敏感。