Tissue-resident memory CD8⁺ T cells (T_RM) constitute a noncirculating memory T cell subset that provides early protection against reinfection. However, how T_RM arise from antigen-triggered T cells has remained unclear. Exploiting the T_RM-restricted expression of Hobit, we used T_RM reporter/deleter mice to study T_RM differentiation. We found that Hobit was up-regulated in a subset of LCMV-specific CD8⁺ T cells located within peripheral tissues during the effector phase of the immune response. These Hobit⁺ effector T cells were identified as T_RM precursors, given that their depletion substantially decreased T_RM development but not the formation of circulating memory T cells. Adoptive transfer experiments of Hobit⁺ effector T cells corroborated their biased contribution to the T_RM lineage. Transcriptional profiling of Hobit⁺ effector T cells underlined the early establishment of T_RM properties including down-regulation of tissue exit receptors and up-regulation of T_RM-associated molecules. We identified Eomes as a key factor instructing the early bifurcation of circulating and resident lineages. These findings establish that commitment of T_RM occurs early in antigen-driven T cell differentiation and reveal the molecular mechanisms underlying this differentiation pathway.

组织驻留记忆 CD8 ⁺ T 细胞 (T _RM ) 构成非循环记忆 T 细胞亚群，可提供早期保护以防止再感染。然而，T _RM如何由抗原触发的 T 细胞产生仍不清楚。利用Hobit的 T _{RM限制性表达，我们使用 T RM}报告/删除小鼠来研究 T _RM分化。我们发现，在免疫反应的效应期，Hobit 在位于外周组织内的一部分 LCMV 特异性 CD8 ^{+ T 细胞中被上调。}这些 Hobit ⁺效应 T 细胞被鉴定为 T _RM前体，因为它们的消耗大大减少了 T _RM的发展，但没有减少循环记忆 T 细胞的形成。Hobit ^{+效应 T 细胞的过继转移实验证实了它们对 T} _RM谱系的偏向贡献。Hobit ^{+效应 T 细胞的转录谱强调了 T} _RM特性的早期建立，包括组织出口受体的下调和 T _RM相关分子的上调。我们将 Eomes 确定为指导循环和常驻血统早期分叉的关键因素。这些发现确立了 T _RM的承诺发生在抗原驱动的 T 细胞分化的早期，并揭示了这种分化途径的分子机制。