Tissue-resident memory T cells (TRMs) are a novel nonvascular memory T cell subset. Although CD8⁺ TRMs are well-characterized, CD4⁺ TRMs-especially lung-resident memory Th17 cells-are still being defined. In this study, we characterized lung-resident memory Th17 cells (lung TRM17) and their role in protection against the highly virulent fungus Cryptococcus gattii. We found that intravenously transferred DCs preferentially migrated to lungs and attracted recipient DCs and led to the induction of long-lived Th17 cells expressing characteristic markers. This population could be clearly discriminated from circulating T cells by intravascular staining and was not depleted by the immunosuppressive agent FTY720. The C. gattii antigen re-stimulation assay revealed that vaccine-induced lung Th17 cells produced IL-17A but not IFNγ. The DC vaccine significantly increased IL-17A production and suppressed fungal burden in the lungs and improved the survival of mice infected with C. gattii. This protective effect was significantly reduced in the IL-17A knockout (KO) mice, but not in the FTY720-treated mice. The protective effect also coincided with the activation of neutrophils and multinucleated giant cells, and these inflammatory responses were suppressed in the vaccinated IL-17A KO mice. Overall, these data demonstrated that the systemic DC vaccine induced lung TRM17, which played a substantial role in anti-fungal immunity.

中文翻译：

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基于树突细胞的全身性疫苗可诱导长寿命的肺驻留记忆 Th17 细胞并改善肺部真菌病。

组织驻留记忆 T 细胞 (TRM) 是一种新型非血管记忆 T 细胞亚群。虽然 CD8 ⁺ TRM 的特征很明确，但 CD4 ⁺TRM——尤其是肺驻留记忆 Th17 细胞——仍在定义中。在这项研究中，我们描述了肺驻留记忆 Th17 细胞（肺 TRM17）及其在抵御高毒性真菌格特隐球菌中的作用。我们发现静脉内转移的 DC 优先迁移到肺部并吸引受体 DC，并导致诱导表达特征标记的长寿 Th17 细胞。这个群体可以通过血管内染色与循环 T 细胞清楚地区分，并且没有被免疫抑制剂 FTY720 耗尽。C. gattii 抗原再刺激试验表明疫苗诱导的肺 Th17 细胞产生 IL-17A 但不产生 IFNγ。DC 疫苗显着增加了 IL-17A 的产生并抑制了肺部的真菌负荷，并提高了感染格特梭菌的小鼠的存活率。这种保护作用在 IL-17A 敲除 (KO) 小鼠中显着降低，但在 FTY720 处理的小鼠中没有。保护作用还与中性粒细胞和多核巨细胞的激活同时发生，并且这些炎症反应在接种疫苗的 IL-17A KO 小鼠中受到抑制。总的来说，这些数据表明全身性 DC 疫苗诱导了肺 TRM17，它在抗真菌免疫中发挥了重要作用。