title: Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.
abstract: BACKGROUND
  In human subjects, allergen tolerance has been observed after high-dose allergen exposure or after completed allergen immunotherapy, which is related to the accumulation of anti-inflammatory IgG4. However, the specific T-cell response that leads to IgG4 induction during chronic allergen exposure remains poorly understood.
  
  
  OBJECTIVE
  We sought to evaluate the relationship between cat allergen-specific T-cell frequency, cat allergen-specific IgE and IgG4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG4 is produced.
  
  
  METHODS
  Fel d 1-, Fel d 4-, Fel d 7-, and Fel d 8-specific T-cell responses were characterized by CD154 expression after antigen stimulation.
  
  
  RESULTS
  In allergic subjects without cat ownership, the frequency of cat allergen (Fel d 1 and Fel d 4)-specific TH2 (sTH2) cells correlates with higher IgE levels and is linked to asthma. Paradoxically, we observed that subjects with cat allergy and chronic cat exposure maintain a high frequency of sTH2 cells, which correlates with higher IgG4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG4 after cognate interactions with sTH2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein.
  
  
  CONCLUSIONS
  These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG4 are present in allergic subjects and (2) cat allergen exposure induces an IgG4 response in a TH2 cell-dependent manner. Thus IgG4 accumulation could be mediated by chronic activation of the TH2 response, which in turn drives desensitization.
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash.
authors.forename: Amedee
authors.initials: A
authors.lastname: Renand
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash.
authors.forename: Luis D
authors.initials: LD
authors.lastname: Archila
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash.
authors.forename: John
authors.initials: J
authors.lastname: McGinty
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash.
authors.forename: Erik
authors.initials: E
authors.lastname: Wambre
authors.affiliation: the Asthma and Allergy Department, Virginia Mason Medical Center, Seattle, Wash.
authors.forename: David
authors.initials: D
authors.lastname: Robinson
authors.affiliation: Telethon Kids Institute, University of Western Australia, Subiaco, Australia.
authors.forename: Belinda J
authors.initials: BJ
authors.lastname: Hales
authors.affiliation: Telethon Kids Institute, University of Western Australia, Subiaco, Australia.
authors.forename: Wayne R
authors.initials: WR
authors.lastname: Thomas
authors.affiliation: Benaroya Research Institute at Virginia Mason, Seattle, Wash; Department of Medicine, University of Washington, Seattle, Wash. Electronic address: bkwok@benaroyaresearch.org.
authors.forename: William W
authors.initials: WW
authors.lastname: Kwok
mesh_terms: D000328:Adult; D000368:Aged; D000485:Allergens / Q000276:immunology*; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D002415:Cats / Q000276:immunology*; D006801:Humans; D006967:Hypersensitivity / Q000097:blood / Q000276:immunology*; D007073:Immunoglobulin E / Q000097:blood; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D008875:Middle Aged; D012882:Skin Tests; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000485:Allergens; D007074:Immunoglobulin G; D007073:Immunoglobulin E
keywords: CD154; Cat allergy; Fel d 1; Fel d 4; IgG(4); T(H)2 cells; allergen exposure; allergen tolerance; asthma; class II tetramer