Sensitization with Fungal Protease Allergen Establishes Long-Lived, Allergenic Th Cell Memory in the Lung
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...
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| Published in: | The Journal of immunology (1950) Vol. 212; no. 9; pp. 1420 - 1427 |
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| Main Authors: | , , , , , , |
| Format: | Journal Article |
| Language: | English |
| Published: |
United States
01-05-2024
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| Online Access: | Get full text |
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| Summary: | 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. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 |
| ISSN: | 0022-1767 1550-6606 |
| DOI: | 10.4049/jimmunol.2300694 |