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

Immunity. 2016 Jan 19;44(1):155-166. doi: 10.1016/j.immuni.2015.11.004. Epub 2015 Dec 29.

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.

MeSH terms

  • Allergens / immunology
  • Animals
  • Antigens, Dermatophagoides / immunology
  • Asthma / immunology*
  • Cell Differentiation / immunology
  • Cell Separation
  • Disease Models, Animal
  • Female
  • Immunologic Memory / immunology*
  • Interleukin-2 / immunology*
  • Lung / immunology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Pyroglyphidae / immunology
  • Th2 Cells / immunology*

Substances

  • Allergens
  • Antigens, Dermatophagoides
  • Interleukin-2