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

• Published in: Journal of allergy and clinical immunology Vol. 150; no. 6; pp. 1415 - 1426.e9
• Main Authors: Agrawal, Komal, Ong, Li Ching, Monkley, Susan, Thörn, Kristofer, Israelsson, Elisabeth, Baturcam, Engin, Rist, Cassie, Schön, Karin, Blake, Sophia, Magnusson, Björn, Cartwright, James, Mitra, Suman, Ravi, Abilash, Zounemat-Kermani, Nazanin, Krishnaswamy, Jayendra Kumar, Lycke, Nils Y., Gehrmann, Ulf, Mattsson, Johan
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-12-2022
• Subjects: Allergens; Animals; Asthma; CD8-Positive T-Lymphocytes; exacerbations; Humans; IFN-γ; influenza infection; Influenza, Human; Lung; Lungmedicin och allergi; Memory T Cells; Mice; mouse model; Respiratory Medicine and Allergy; tissue resident memory T (TRM) cells; HDM; hi; IFN-γ; NP; influenza infection; mouse model; exacerbations; U-BIOPRED; HA; tissue resident memory T (TRM) cells; TRM; Asthma
• ISSN: 0091-6749; 1097-6825
• DOI: 10.1016/j.jaci.2022.07.004

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.
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