T cell epitope-specific defects in the immune response to cat allergen in patients with atopic dermatitis

Abstract

Atopic dermatitis (AD) is often associated with high titer IgE antibodies (ab) to allergens, and IL-10-mediated regulation of IFN-γ has been proposed to contribute to this IgE ab production. However, the relevance of IL-10 and IFN-γ to IgE associated with AD has not been examined in the context of an allergen-specific system. Analysis of PBMC responses in vitro showed deficient T cell proliferation to overlapping IL-10- (peptide (P) 2:1) and IFN-γ-(P2:2) inducing chain 2 major epitopes of cat allergen (FeI d 1) in cultures from sensitized AD patients (mean IgE to cat = 20.9 IU/ml). Diminished IFN-γ induction by FeI d 1 and P2:2, along with elevated peptide-induced IL-10 (except for P2:1) was observed in PBMC cultures from AD subjects compared with non-AD (sensitized and non-sensitized) subjects. Neither T cell proliferation nor IFN-γ production to chain 2 epitopes could be restored by anti-IL-10 mAb in cultures from sensitized AD subjects. Moreover, allergen avoidance was associated with a paradoxical decrease in both IL-10 and IFN-γ in peptide-stimulated PBMC from these subjects. Control of IFN-γ production to chain 2 epitopes by IL-10 may be relevant to sensitization status. Development of high titer IgE ab in AD could reflect a failure of this mechanism.