Properties of Circulating Regulatory T Cells Associated with Nascent IgE Responses in Children with Atopic Dermatitis

Abstract

RATIONALE: Atopic dermatitis (AD) is associated with increased circulating CD25hi regulatory T cells (Tregs) which comprise CCR6+ and CCR6neg subsets. We aim to monitor Tregs in early life and identify serum cytokine patterns which predict expansion of these cells, increased total IgE levels and persistent disease. METHODS: Children (5 months to 14 years, n=13) presenting with eczematous skin eruption were evaluated for disease severity (SCORAD). Measurement of serum IgE (CAP assay) and cytokines/chemokines (27-Plex cytometric bead assay or ELISA) was performed. PBMCs were analyzed by flow cytometry for expression of surface antigens and Foxp3 protein. RESULTS: Elevated levels of factors implicated in altered Treg homeostasis or function (IL-1, IL-2, IL-6, and IL-15) were measurable in early life in a subset of children. Levels of AD-associated chemokines (CCL17 and CCL18) were highly variable in early life and, in contrast to adult patients, did not correlate with total IgE titers. Children >24 months exhibited markedly increased total IgE compared with younger children (mean=4,260 IU/ml [n=5] vs. 30.2 IU/ml [n=8]) and this reflected a shift from an IgE ab profile directed against foods, to one dominated by inhalant allergens. Evidence for expansion of CD25hi Tregs (>79% Foxp3+) was present in 2 of 3 children (ages 4 and 13 years) with moderate/severe AD, with these cells constituting 5.1% and 8.6% of total CD4+ T cells. However, the proportion of memory Tregs which expressed CCR6 was diminished compared with adults. CONCLUSIONS: Our findings demonstrate the feasibility of evaluating altered Treg homeostasis associated with nascent allergen-specific responses in AD.