Center for Immunity and Inflammation, NJ Medical School, Rutgers-The State University of New Jersey, Newark, NJ.
Department of Medicine, NJ Medical School, Rutgers-The State University of New Jersey, Newark, NJ.
J Immunol. 2024 May 1;212(9):1420-1427. doi: 10.4049/jimmunol.2300694.
Allergic asthma is a chronic inflammatory disease that affects millions of individuals worldwide. Exposure to allergens produced by a variety of otherwise harmless microbes, including fungi, predisposes individuals to immunopathologic disease upon subsequent encounters with allergen. We developed a mouse model that employs a purified protease produced by Aspergillus (Asp f 13) to investigate the contributions of CD4+ Th cells to recurrent lung inflammation. Notably, memory CD4+ T cells enhanced the eosinophil response of sensitized/rechallenged animals. In addition, memory CD4+ T cells maintained allergenic features, including expression of GATA-binding protein 3 and IL-5. Th2 memory T cells persisted in the peribronchiolar interstitium of the lung and expressed markers of tissue residence, such as CD69, CCR8, and IL-33R. Lastly, we identified a peptide epitope contained within Asp f 13 and generated a peptide-MHC class II tetramer. Using these tools, we further demonstrated the durability and exquisite sensitivity of memory T cells in promoting lung eosinophilia. Our data highlight important features of memory T cells that strengthen the notion that memory T cells are principal drivers of eosinophilic disease in murine models of allergic sensitization and episodic airway inflammation.
变应性哮喘是一种慢性炎症性疾病，影响着全球数以百万计的人。暴露于各种原本无害的微生物（包括真菌）产生的过敏原，会使个体在随后遇到过敏原时易患免疫病理疾病。我们开发了一种小鼠模型，该模型使用曲霉（Asp f 13）产生的一种纯化蛋白酶来研究 CD4+Th 细胞对复发性肺部炎症的贡献。值得注意的是，记忆性 CD4+T 细胞增强了致敏/再挑战动物的嗜酸性粒细胞反应。此外，记忆性 CD4+T 细胞保持了变应原特征，包括 GATA 结合蛋白 3 和 IL-5 的表达。Th2 记忆 T 细胞在肺的细支气管周围间质中持续存在，并表达组织驻留标志物，如 CD69、CCR8 和 IL-33R。最后，我们鉴定了 Asp f 13 中包含的肽表位，并生成了肽-MHC 类二聚体。使用这些工具，我们进一步证明了记忆 T 细胞在促进肺嗜酸性粒细胞增多方面的持久性和高度敏感性。我们的数据突出了记忆 T 细胞的重要特征，强化了记忆 T 细胞是变应性致敏和间歇性气道炎症的小鼠模型中嗜酸性粒细胞疾病的主要驱动因素的观点。
