title: Staphylococcal enterotoxin A-activated regulatory T cells promote allergen-specific TH2 response to intratracheal allergen inoculation.
abstract: TH2 responses are implicated in asthma pathobiology. Epidemiologic studies have found a positive association between asthma and exposure to staphylococcal enterotoxins.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  SEA promoted TH2 responses of allergen-specific T cells and asthma pathogenesis by activating Treg cells.
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV; Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV; Center for Cell Development and Differentiation, Department of Biology, College of Science, Marshall University, Huntington, WV. Electronic address: zengw@marshall.edu.
authors.forename: Wei-Ping
authors.initials: WP
authors.lastname: Zeng
authors.affiliation: Department of Biochemistry and Microbiology, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
authors.forename: Margaret M
authors.initials: MM
authors.lastname: McFarland
authors.affiliation: HB Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, Ind.
authors.forename: Baohua
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Institute of Immunology and Transfusion Medicine, University Medicine Greifswald, Greifswald, Germany.
authors.forename: Silva
authors.initials: S
authors.lastname: Holtfreter
authors.affiliation: Department of Pediatrics, Joan C. Edwards School of Medicine, Marshall University, Huntington, WV.
authors.forename: Susan
authors.initials: S
authors.lastname: Flesher
authors.affiliation: Department of Microbiology and Immunology, Geisel School of Medicine, Dartmouth University, Hanover, NH.
authors.forename: Ambrose
authors.initials: A
authors.lastname: Cheung
authors.affiliation: Department of Mathematics, College of Science, Marshall University, Huntington, WV.
authors.forename: Avishek
authors.initials: A
authors.lastname: Mallick
mesh_terms: D000485:Allergens / Q000276:immunology; D000818:Animals; D001249:Asthma / Q000276:immunology*; D002454:Cell Differentiation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014132:Trachea / Q000378:metabolism
chemical_list: D000485:Allergens; D004768:Enterotoxins; D018793:Interleukin-13; D015847:Interleukin-4; C026066:enterotoxin A, Staphylococcal; D007371:Interferon-gamma; D010047:Ovalbumin
keywords: Asthma; T(H)2 cells; regulatory T cells; staphylococcal enterotoxin