Resolution of Der p1-induced allergic airway inflammation is dependent on CD4+CD25+Foxp3+ regulatory cells

Melanie D Leech, Robert A Benson, Annick De Vries, Paul M Fitch, Sarah E M Howie

Research output: Contribution to journalArticlepeer-review

Abstract

Allergic airway inflammation (AAI) is characterized by airway hyperreactivity, eosinophilia, goblet cell hyperplasia, and elevated serum IgE, however, it is unclear what mediates natural resolution after cessation of allergen exposure. This is important because the outcome of subsequent allergen challenge may depend on the concurrent inflammatory milieu of the lung. Using a murine AAI model, we demonstrate that after exposure to a defined natural protein allergen, Der p1, the response in lungs and draining mediastinal lymph nodes (dMLN) peaks between 4 and 6 days then declines until resolution by 21 days. Der p1-specific serum IgE follows the same pattern while IgG1 continues to increase. Resolution of AAI is mediated by CD4(+)CD25(+)Foxp3(+) regulatory T cells (Tregs), which appear in lungs and dMLN following airway challenge. Treg depletion exacerbated lung eosinophilia, increased dMLN IL-5 and IL-13 but not IL-10 secretion, and increased allergic Ab responses. Most convincingly, transfer of CD4(+)CD25(+)Foxp3(+) T cells from Ag naive mice (natural Tregs) abolished AAI, decreased dMLN IL-5 and IL-13 secretion, increased dMLN IL-10 secretion, abolished IgE, and decreased IgG1 Abs. Blocking IL-10 receptor function in vivo did not block the anti-inflammatory function of transferred natural Tregs but did restore dMLN IL-5 and IL-13 secretion. Thus natural Tregs can control AAI in an IL-10 independent manner.
Original languageEnglish
Pages (from-to)7050-8
Number of pages9
JournalJournal of Immunology
Volume179
Issue number10
Publication statusPublished - 15 Nov 2007

Keywords

  • Animals
  • Antibody Formation
  • Antigens, Dermatophagoides
  • Arthropod Proteins
  • Asthma
  • Cysteine Endopeptidases
  • Cytokines
  • Eosinophilia
  • Goblet Cells
  • Hyperplasia
  • Immunoglobulin E
  • Inflammation
  • Lung
  • Lymph Nodes
  • Mice
  • Receptors, Interleukin-10
  • T-Lymphocytes, Regulatory

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