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

Brian D. Hondowicz, Dowon An, Jason M. Schenkel, Karen S. Kim, Holly R. Steach, Akshay T. Krishnamurty, Gladys J. Keitany, Esteban N. Garza, Kathryn A. Fraser, James J. Moon, William A. Altemeier, David Masopust, Marion Pepper

Research output: Contribution to journalArticlepeer-review

135 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)155-166
Number of pages12
JournalImmunity
Volume44
Issue number1
DOIs
StatePublished - Jan 19 2016

Bibliographical note

Funding Information:
We thank Dr. Dent, Dr. McKenzie, Dr. Lira, and Dr. Mohrs for mice. We thank Andre Han for assistance with tetramer production. We are grateful to Drs. Bevan and Jenkins for reviewing the manuscript.

Publisher Copyright:
© 2016 Elsevier Inc.

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