Chronic cat allergen exposure induces a TH2 cell-dependent IgG4 response related to low sensitization.

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 IgG 4 . However, the specific T-cell response that leads to IgG 4 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 IgG 4 titers, and clinical status in adults with cat allergy with and without cat ownership and the cellular mechanism by which IgG 4 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 T H 2 (sT H 2) 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 sT H 2 cells, which correlates with higher IgG 4 levels and low sensitization. B cells from allergic, but not nonallergic subjects, are able to produce IgG 4 after cognate interactions with sT H 2 clones and Fel d 1 peptide or the Fel d 1 recombinant protein. Conclusion These experiments suggest that (1) allergen-experienced B cells with the capacity to produce IgG 4 are present in allergic subjects and (2) cat allergen exposure induces an IgG 4 response in a T H 2 cell–dependent manner. Thus IgG 4 accumulation could be mediated by chronic activation of the T H 2 response, which in turn drives desensitization.