The mechanisms that guide T helper 2 (T_H2) cell differentiation in barrier tissues are unclear. Here we describe the molecular pathways driving allergen-specific T_H2 cells using temporal, spatial and single-cell transcriptomic tracking of house dust mite-specific T cells in mice. Differentiation and migration of lung allergen-specific T_H2 cells requires early expression of the transcriptional repressor Blimp-1. Loss of Blimp-1 during priming in the lymph node ablated the formation of T_H2 cells in the lung, indicating early Blimp-1 promotes T_H2 cells with migratory capability. IL-2/STAT5 signals and autocrine/paracrine IL-10 from house dust mite-specific T cells were essential for Blimp-1 and subsequent GATA3 upregulation through repression of Bcl6 and Bach2. Spatial microniches of IL-2 in the lymph node supported the earliest Blimp-1⁺T_H2 cells, demonstrating lymph node localization is a driver of T_H2 initiation. Our findings identify an early requirement for IL-2-mediated spatial microniches that integrate with allergen-driven IL-10 from responding T cells to drive allergic asthma.

指导屏障组织中辅助性 T 细胞 2 （T_H2） 分化的机制尚不清楚。在这里，我们使用小鼠屋尘螨特异性 T 细胞的时间、空间和单细胞转录组学跟踪来描述驱动过敏原特异性 T_H2 细胞的分子途径。肺过敏原特异性 T_H2 细胞的分化和迁移需要转录抑制因子 Blimp-1 的早期表达。在淋巴结中引发过程中 Blimp-1 的丢失消融了肺中 T_H2 细胞的形成，表明早期 Blimp-1 促进了具有迁移能力的 T_H2 细胞。来自屋尘螨特异性 T 细胞的 IL-2/STAT5 信号和自分泌/旁分泌 IL-10 对于通过抑制 Bcl6 和 Bach2 上调 Blimp-1 和随后的 GATA3 上调至关重要。淋巴结中 IL-2 的空间微生态位支持最早的 Blimp-1⁺T_H2 细胞，表明淋巴结定位是 T_H2 起始的驱动因素。我们的研究结果确定了 IL-2 介导的空间微生态位的早期需求，这些微生态位与过敏原驱动的 IL-10 整合，来自反应性 T 细胞以驱动过敏性哮喘。