Analysis of CD25 hiCD4 + “regulatory” T-cell subtypes in atopic dermatitis reveals a novel T H2-like population

Abstract

It is unresolved whether circulating CD25hiCD4+ T cells in patients with atopic dermatitis who have elevated IgE (IgE(high)) are regulatory or effector in nature. To analyze the properties of CD25hi T-cell subtypes in IgE(high) atopic dermatitis. The phenotype of circulating CD25hi T cells was analyzed by flow cytometry using PBMCs from patients with atopic dermatitis (total IgE > 250 IU/mL). Cytokines induced in CD25hi subtypes were analyzed after activation with anti-CD3 mAb (+/-IL-2) and in the presence of activated autologous effector T cells (CD25negCD4+). Reactivity to bacterial superantigen derived from the skin-colonizing organism Staphylococcus aureus was also evaluated. CD25(hi) T cells expressing regulatory T-cell markers (Foxp3, CCR4, cutaneous lymphocyte-associated antigen) were increased in atopic dermatitis compared with IgE(low) controls. This phenomenon was linked to disease severity. Two subtypes of CD25hi T cells were identified on the basis of differential expression of the chemokine receptor CCR6. Although the ratio of CCR6+ and CCR6neg subtypes within the CD25hi subset was unaltered in atopic dermatitis, each subtype proliferated spontaneously ex vivo, suggesting in vivo activation. Activated CCR6neg cells secreted T(H)2 cytokines, and coculture with effector T cells selectively enhanced IL-5 production. Moreover, induction of a T(H)2-dominated cytokine profile on activation with bacterial superantigen was restricted to the CCR6neg subtype. Despite a regulatory phenotype, activated CD25hi T cells that lack expression of CCR6 promote T(H)2 responses.