Background

Chronic airway diseases such as asthma are characterized by persistent type 2 immunity in the airways. We know little about the mechanisms that explain why type 2 inflammation continues in these diseases.

Objective

We used mouse models to investigate the mechanisms involved in long-lasting immune memory.

Methods

Naive mice were exposed intranasally to ovalbumin (OVA) antigen with Alternaria extract as an adjuvant. Type 2 memory was analyzed by parabiosis model, flow cytometry with in vivo antibody labeling, and intranasal OVA recall challenge. Gene-deficient mice were used to analyze the mechanisms.

Results

In the parabiosis model, mice previously exposed intranasally to OVA with Alternaria showed more robust antigen-specific immune responses and airway inflammation than mice with circulating OVA-specific T cells. After a single airway exposure to OVA with Alternaria, CD69⁺ST2⁺ T_H2-type T cells, which highly express type 2 cytokine messenger RNA and lack CD62L expression, appeared in lung tissue within 5 days and persisted for at least 84 days. When exposed again to OVA in vivo, these cells produced type 2 cytokines quickly without involving circulating T cells. Development of tissue-resident CD69⁺ST2⁺ T_H2 cells and long-term memory to an inhaled antigen were abrogated in mice deficient in ST2 or IL-33, but not TSLP receptor.

Conclusion

CD69⁺ST2⁺ T_H2 memory cells develop quickly in lung tissue after initial allergen exposure and persist for a prolonged period. The ST2/IL-33 pathway may play a role in the development of immune memory in lung to certain allergens.

中文翻译：

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肺驻留 CD69+ST2+ TH2 细胞介导小鼠对吸入抗原的长期 2 型记忆

背景

哮喘等慢性气道疾病的特点是气道中持续存在 2 型免疫。我们对解释为什么 2 型炎症在这些疾病中持续存在的机制知之甚少。

客观的

我们使用小鼠模型来研究持久免疫记忆的机制。

方法

将首次实验的小鼠鼻内暴露于卵清蛋白 (OVA) 抗原，并以链格孢提取物作为佐剂。通过联体共生模型、体内抗体标记的流式细胞术和鼻内 OVA 回忆挑战来分析 2 型记忆。使用基因缺陷小鼠来分析其机制。

结果

在联体共生模型中，之前鼻内暴露于含有链格孢属的 OVA 的小鼠比具有循环 OVA 特异性T 细胞的小鼠表现出更强烈的抗原特异性免疫反应和气道炎症。单次气道暴露于含有链格孢的 OVA 后，CD69 ⁺ ST2 ⁺ T _H 2 型 T 细胞高度表达 2 型细胞因子信使 RNA，但缺乏 CD62L 表达，在 5 天内出现在肺组织中，并持续至少 84 天。当在体内再次暴露于 OVA 时，这些细胞迅速产生 2 型细胞因子，而不涉及循环 T 细胞。组织驻留 CD69 ⁺ ST2 ⁺ T _H的开发ST2 或 IL-33 缺陷小鼠的 2 细胞和对吸入抗原的长期记忆被消除，但 TSLP 受体却没有。

结论

CD69 ⁺ ST2 ⁺ T _H 2 记忆细胞在初次接触过敏原后在肺组织中快速发育并持续较长时间。ST2/IL-33 通路可能在肺部对某些过敏原的免疫记忆的形成中发挥作用。