Analysis of CD25^hiCD4⁺ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel T_H2-like population

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• 作者：Am ; a J. Reefer ; Shama M. Satinover ; Michael D. Solga ; Joanne A. Lannigan ; Jennifer T. Nguyen ; Barbara B. Wilson ; Judith A. Woodfolk
• 关键词：Human regulatory T cells ; T_H2 cytokines ; CCR4 ; CLA ; CCR6 ; CD25 ; Foxp3 ; bacterial superantigen ; allergen avoidance
• 刊名：Journal of Allergy and Clinical Immunology
• 出版年：2008
• 出版时间：February 2008
• 年：2008
• 卷：121
• 期：2
• 页码：415-422.e3
• 全文大小：1513 K

文摘

Background

It is unresolved whether circulating CD25^hiCD4⁺ T cells in patients with atopic dermatitis who have elevated IgE (IgE^high) are regulatory or effector in nature.

Objective

To analyze the properties of CD25^hi T-cell subtypes in IgE^high atopic dermatitis.

Methods

The phenotype of circulating CD25^hi T cells was analyzed by flow cytometry using PBMCs from patients with atopic dermatitis (total IgE > 250 IU/mL). Cytokines induced in CD25^hi subtypes were analyzed after activation with anti-CD3 mAb (±IL-2) and in the presence of activated autologous effector T cells (CD25^negCD4⁺). Reactivity to bacterial superantigen derived from the skin-colonizing organism Staphylococcus aureus was also evaluated.

Results

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 CD25^hi T cells were identified on the basis of differential expression of the chemokine receptor CCR6. Although the ratio of CCR6⁺ and CCR6^neg subtypes within the CD25^hi subset was unaltered in atopic dermatitis, each subtype proliferated spontaneously ex vivo, suggesting in vivo activation. Activated CCR6^neg cells secreted T_H2 cytokines, and coculture with effector T cells selectively enhanced IL-5 production. Moreover, induction of a T_H2-dominated cytokine profile on activation with bacterial superantigen was restricted to the CCR6^neg subtype.

Conclusion

Despite a regulatory phenotype, activated CD25^hi T cells that lack expression of CCR6 promote T_H2 responses.