Atopic dermatitis and skin disease
Analysis of CD25hiCD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel TH2-like population

https://doi.org/10.1016/j.jaci.2007.11.003Get rights and content

Background

It is unresolved whether circulating CD25hiCD4+ T cells in patients with atopic dermatitis who have elevated IgE (IgEhigh) are regulatory or effector in nature.

Objective

To analyze the properties of CD25hi T-cell subtypes in IgEhigh atopic dermatitis.

Methods

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.

Results

CD25hi T cells expressing regulatory T-cell markers (Foxp3, CCR4, cutaneous lymphocyte-associated antigen) were increased in atopic dermatitis compared with IgElow 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 TH2 cytokines, and coculture with effector T cells selectively enhanced IL-5 production. Moreover, induction of a TH2-dominated cytokine profile on activation with bacterial superantigen was restricted to the CCR6neg subtype.

Conclusion

Despite a regulatory phenotype, activated CD25hi T cells that lack expression of CCR6 promote TH2 responses.

Section snippets

Subjects

Patients with AD were diagnosed by using the criteria of Hanifin and Rajka.18 T-cell studies were performed in 14 patients with AD (13 adults ages 19-53 years and 1 child, age 13 years) with high total IgE (≥250 IU/mL) and a clinical history of early disease onset (age < 1 year). Severity of disease was assessed by the Scoring Atopic Dermatitis (SCORAD) index.19 Healthy subjects without AD (ages 24-46 years; n = 14) who had low total IgE (<140 IU/mL) and reported no allergic symptoms were IgElow

Increased circulating CD25hiCD4+ T cells in patients with AD exhibit a surface phenotype consistent with skin-homing regulatory T cells

The properties of circulating CD25hiCD4+ T cells were compared in IgEhigh patients with AD and IgElow healthy controls (Table I). By using 7-color flow cytometry staining, we analyzed tissue-homing receptors normally expressed on CD25hi regulatory T cells in healthy individuals.12, 13, 20, 21, 22 Almost all CD4+ T cells that expressed the highest levels of CD25 also expressed the chemokine receptor CCR4 regardless of disease status (Fig 1, A; see this article's Fig E1 in the Online Repository

Discussion

We have identified a novel CD25hiCD4+ T-cell subtype with TH2-like properties in patients with AD. This subtype exhibits a phenotype characteristic of CD25hi regulatory T cells (CLA+CCR4+Foxp3+) but lacks expression of the chemokine receptor CCR6. Despite the capacity for whole CD25hiCD4+ T  cells from patients with AD to suppress autologous effector T cells, the CD25hiCCR6neg T-cell subtype exhibited TH2-promoting properties as judged by (1) increased production of TH2 cytokines compared with

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  • Cited by (0)

    Supported by National Institutes of Health RO1 grants AI-052196 and AI-020565 and by a grant to the University of Virginia General Clinical Research Center, 5 MO1 RR00847.

    Disclosure of potential conflict of interest: J. A. Woodfolk has consultant arrangements with EpiVax Inc. The rest of the authors have declared that they have no conflict of interest.

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