Staphylococcal enterotoxin A–activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation

Wei ping Zeng, Margaret M. McFarland, Baohua Zhou, Silva Holtfreter, Susan Flesher, Ambrose Cheung, Avishek Mallick

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Background TH2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins. Objective We used a mouse model of asthma to determine whether staphylococcal enterotoxins promote TH2 differentiation of allergen-specific CD4 conventional T (Tcon) cells and asthma by activating allergen-nonspecific regulatory T (Treg) cells to create a TH2-polarizing cytokine milieu. Methods Ovalbumin (OVA)–specific, staphylococcal enterotoxin A (SEA)–nonreactive naive CD4 Tcon cells were cocultured with SEA-reactive allergen-nonspecific Treg or CD4 Tcon cells in the presence of OVA and SEA. The OVA-specific CD4 T cells were then analyzed for IL-13 and IFN-γ expression. SEA-activated Treg cells were analyzed for the expression of the TH2-polarizing cytokine IL-4 and the T-cell activation markers CD69 and CD62L. For asthma induction, mice were intratracheally sensitized with OVA or cat dander extract (CDE) alone or together with SEA and then challenged with OVA or CDE. Mice were also subject to transient Treg cell depletion before sensitization with OVA plus SEA. Asthma features and TH2 differentiation in these mice were analyzed. Results SEA-activated Treg cells induced IL-13 but suppressed IFN-γ expression in OVA-specific CD4 Tcon cells. SEA-activated Treg cells expressed IL-4, upregulated CD69, and downregulated CD62L. Sensitization with OVA plus SEA but not OVA alone induced asthma, and SEA exacerbated asthma induced by CDE. Depletion of Treg cells abolished these effects of SEA and IL-13 expression in OVA-specific T cells. Conclusion SEA promoted TH2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells.

Original languageEnglish (US)
Pages (from-to)508-518.e4
JournalJournal of Allergy and Clinical Immunology
Volume139
Issue number2
DOIs
StatePublished - Feb 1 2017

Keywords

  • Asthma
  • T2 cells
  • regulatory T cells
  • staphylococcal enterotoxin

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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