Tissue-resident memory T cells (T_RM) provide optimal defense at the sites of infection, but signals regulating their development are unclear, especially for CD4 T cells. Here we identify two distinct pathways that lead to the generation of CD4 T_RM in the lungs following influenza infection. The T_RM are transcriptionally distinct from conventional memory CD4 T cells and share a gene signature with CD8 T_RM. The CD4 T_RM are superior cytokine producers compared with conventional memory cells, can protect otherwise naive mice against a lethal influenza challenge, and display functional specialization by inducing enhanced inflammatory responses from dendritic cells compared with conventional memory cells. Finally, we demonstrate than an interleukin (IL)-2-dependent and a novel IL-2-independent but IL-15-dependent pathway support the generation of cohorts of lung T_RM.

中文翻译：

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IL-15 支持产生保护性肺驻留记忆 CD4 T 细胞。

组织驻留记忆 T 细胞 ( _TRM ) 在感染部位提供最佳防御，但调节其发育的信号尚不清楚，尤其是对于 CD4 T 细胞。在这里，我们确定了导致流感感染后肺部产生 CD4 T _{RM的两种不同途径。}T _RM在转录上不同于传统的记忆 CD4 T 细胞，并与 CD8 T _RM共享基因特征。CD4 T _RM与传统记忆细胞相比，它们是更好的细胞因子生产者，可以保护幼稚小鼠免受致命流感的攻击，并通过诱导树突状细胞与传统记忆细胞相比增强的炎症反应来显示功能特化。最后，我们证明白细胞介素 (IL)-2 依赖性和新型 IL-2 非依赖性但 IL-15 依赖性通路支持肺 T _RM队列的产生。