Pathogens and vaccines that produce persisting antigens can generate expanded pools of effector memory CD8⁺ T cells, described as memory inflation. While properties of inflating memory CD8⁺ T cells have been characterized, the specific cell types and tissue factors responsible for their maintenance remain elusive. Here, we show that clinically applied adenovirus vectors preferentially target fibroblastic stromal cells in cultured human tissues. Moreover, we used cell-type-specific antigen targeting to define critical cells and molecules that sustain long-term antigen presentation and T cell activity after adenovirus vector immunization in mice. While antigen targeting to myeloid cells was insufficient to activate antigen-specific CD8⁺ T cells, genetic activation of antigen expression in Ccl19-cre-expressing fibroblastic stromal cells induced inflating CD8⁺ T cells. Local ablation of vector-targeted cells revealed that lung fibroblasts support the protective function and metabolic fitness of inflating memory CD8⁺ T cells in an interleukin (IL)-33-dependent manner. Collectively, these data define a critical fibroblastic niche that underpins robust protective immunity operating in a clinically important vaccine platform.

产生持久性抗原的病原体和疫苗可以产生扩大的效应记忆 CD8 ⁺ T 细胞池，称为记忆膨胀。虽然膨胀记忆 CD8 ⁺ T 细胞的特性已经被表征，但负责维持它们的特定细胞类型和组织因子仍然难以捉摸。在这里，我们显示临床应用的腺病毒载体优先靶向培养的人体组织中的成纤维细胞基质细胞。此外，我们使用细胞类型特异性抗原靶向来定义在小鼠腺病毒载体免疫后维持长期抗原呈递和 T 细胞活性的关键细胞和分子。虽然靶向骨髓细胞的抗原不足以激活抗原特异性 CD8 ⁺T 细胞，在表达Ccl19 - cre的成纤维细胞基质细胞中抗原表达的遗传激活诱导 CD8 ⁺ T 细胞膨胀。对载体靶向细胞的局部消融显示，肺成纤维细胞以白介素 (IL)-33 依赖性方式支持膨胀记忆 CD8 ^{+ T 细胞的保护功能和代谢适应性。}总的来说，这些数据定义了一个关键的成纤维细胞生态位，它支持在临床上重要的疫苗平台中运行的强大保护性免疫。