Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung.
- 2024-05-01
- Journal of immunology (Baltimore, Md. : 1950) 212(9)
- PubMed: 38488501
- DOI: 10.4049/jimmunol.2300694
Study Design
- Population
- mice
- Methods
- Developed a mouse model using Aspergillus protease Asp f 13 to study CD4+ Th cell contributions to lung inflammation.
- Animal Study
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.
Research Insights
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