Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance.

The Journal of allergy and clinical immunology 2022 Dec

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Patients with asthma often suffer from frequent respiratory viral infections and reduced virus clearance. Lung resident memory T cells provide rapid protection against viral reinfections. Because the development of resident memory T cells relies on the lung microenvironment, we investigated the impact of allergen sensitization on the development of virus-specific lung resident memory T cells and viral clearance. Mice were sensitized with house dust mite extract followed by priming with X47 and a subsequent secondary influenza infection. Antiviral memory T-cell response and protection to viral infection was assessed before and after secondary influenza infection, respectively. Gene set variation analysis was performed on data sets from the U-BIOPRED asthma cohort using an IFN-γ-induced epithelial cell signature and a tissue resident memory T-cell signature. Viral loads were higher in lungs of sensitized compared with nonsensitized mice after secondary infection, indicating reduced virus clearance. X47 priming induced fewer antiviral lung resident memory CD8 T cells and resulted in lower pulmonary IFN-γ levels in the lungs of sensitized as compared with nonsensitized mice. Using data from the U-BIOPRED cohort, we found that patients with enrichment of epithelial IFN-γ-induced genes in nasal brushings and bronchial biopsies were also enriched in resident memory T-cell-associated genes, had more epithelial CD8 T cells, and reported significantly fewer exacerbations. The allergen-sensitized lung microenvironment interferes with the formation of antiviral resident memory CD8 T cells in lungs and virus clearance. Defective antiviral memory response might contribute to increased susceptibility of patients with asthma to viral exacerbations. Copyright © 2022 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Citation

Komal Agrawal, Li Ching Ong, Susan Monkley, Kristofer Thörn, Elisabeth Israelsson, Engin Baturcam, Cassie Rist, Karin Schön, Sophia Blake, Björn Magnusson, James Cartwright, Suman Mitra, Abilash Ravi, Nazanin Zounemat-Kermani, Jayendra Kumar Krishnaswamy, Nils Y Lycke, Ulf Gehrmann, Johan Mattsson, U-BIOPRED Study Group. Allergic sensitization impairs lung resident memory CD8 T-cell response and virus clearance. The Journal of allergy and clinical immunology. 2022 Dec;150(6):1415-1426.e9