Lung-resident CD69+ST2+ TH2 cells mediate long-term type 2 memory to inhaled antigen in mice

Takao Kobayashi, Koji Iijima, Koji Matsumoto, Jyoti K. Lama, Hirohito Kita

Research output: Contribution to journalArticlepeer-review


Background: Chronic airway diseases such as asthma are characterized by persistent type 2 immunity in the airways. We know little about the mechanisms that explain why type 2 inflammation continues in these diseases. Objective: We used mouse models to investigate the mechanisms involved in long-lasting immune memory. Methods: Naive mice were exposed intranasally to ovalbumin (OVA) antigen with Alternaria extract as an adjuvant. Type 2 memory was analyzed by parabiosis model, flow cytometry with in vivo antibody labeling, and intranasal OVA recall challenge. Gene-deficient mice were used to analyze the mechanisms. Results: In the parabiosis model, mice previously exposed intranasally to OVA with Alternaria showed more robust antigen-specific immune responses and airway inflammation than mice with circulating OVA-specific T cells. After a single airway exposure to OVA with Alternaria, CD69+ST2+ TH2-type T cells, which highly express type 2 cytokine messenger RNA and lack CD62L expression, appeared in lung tissue within 5 days and persisted for at least 84 days. When exposed again to OVA in vivo, these cells produced type 2 cytokines quickly without involving circulating T cells. Development of tissue-resident CD69+ST2+ TH2 cells and long-term memory to an inhaled antigen were abrogated in mice deficient in ST2 or IL-33, but not TSLP receptor. Conclusion: CD69+ST2+ TH2 memory cells develop quickly in lung tissue after initial allergen exposure and persist for a prolonged period. The ST2/IL-33 pathway may play a role in the development of immune memory in lung to certain allergens.

Original languageEnglish (US)
Pages (from-to)167-181.e6
JournalJournal of Allergy and Clinical Immunology
Issue number1
StatePublished - Jul 2023


  • IL-33
  • IL-5
  • T2 cells
  • allergens
  • allergy
  • tissue-resident memory T cells

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology


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