Interleukin-2-Dependent Allergen-Specific Tissue-Resident Memory Cells Drive Asthma

• Published in: Immunity (Cambridge, Mass.) Vol. 44; no. 1; pp. 155 - 166
• Main Authors: Hondowicz, Brian D., An, Dowon, Schenkel, Jason M., Kim, Karen S., Steach, Holly R., Krishnamurty, Akshay T., Keitany, Gladys J., Garza, Esteban N., Fraser, Kathryn A., Moon, James J., Altemeier, William A., Masopust, David, Pepper, Marion
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.01.2016; Elsevier Limited
• Subjects: Allergens - immunology; Allergies; Amino acids; Animals; Antigens; Antigens, Dermatophagoides - immunology; Asthma - immunology; Bone marrow; Cell Differentiation - immunology; Cell Separation; Chemokines; Cytokines; Dermatophagoides pteronyssinus; Disease Models, Animal; Experiments; Female; Immunologic Memory - immunology; Inflammation; Interleukin-2 - immunology; Lung - immunology; Lungs; Lymphocytes; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Population; Pyroglyphidae - immunology; Th2 Cells - immunology
• ISSN: 1074-7613; 1097-4180; 1097-4180
• DOI: 10.1016/j.immuni.2015.11.004

Exposure to inhaled allergens generates T helper 2 (Th2) CD4+ T cells that contribute to episodes of inflammation associated with asthma. Little is known about allergen-specific Th2 memory cells and their contribution to airway inflammation. We generated reagents to understand how endogenous CD4+ T cells specific for a house dust mite (HDM) allergen form and function. After allergen exposure, HDM-specific memory cells persisted as central memory cells in the lymphoid organs and tissue-resident memory cells in the lung. Experimental blockade of lymphocyte migration demonstrated that lung-resident cells were sufficient to induce airway hyper-responsiveness, which depended upon CD4+ T cells. Investigation into the differentiation of pathogenic Trm cells revealed that interleukin-2 (IL-2) signaling was required for residency and directed a program of tissue homing migrational cues. These studies thus identify IL-2-dependent resident Th2 memory cells as drivers of lung allergic responses. •Allergen-specific CD4+ Th2 memory cells were tracked with MHC class II tetramers•Lung resident memory T cells formed after intranasal house dust mite antigen exposure•IL-2 signaling was required for the formation of lung-resident memory Th2 cells•The lack of BCL-6 expression or B cells promoted T cell entry into the lung The contribution of allergen-specific Th2 memory cells to airway inflammation is not clear. Pepper and colleagues track the development and function of endogenous house dust mite antigen-specific CD4+ T cells and find that pathogenic lung Th2 cells are tissue resident memory cells that depend on IL-2 signaling for their generation.