Authors:
Renand A, Archila LD, McGinty J, Wambre E, Robinson D, Hales BJ, Thomas WR, et al.
Authors notes:
J Allergy Clin Immunol. 2015;136(6):1627-35e13.
Keywords:
Cat allergy, Fel d 1, Fel d 4, TH2 cells, allergen tolerance, asthma, class II tetramer, CD154, IgG4, allergen exposure
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.
Conclusion: These experiments suggest that (1) allergenexperienced 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.