Analysis of CD25hi CD4+ “regulatory” T-cell subtypes in atopic dermatitis reveals a novel TH 2-like population

• Published in: Journal of allergy and clinical immunology Vol. 121; no. 2; pp. 415 - 422.e3
• Main Authors: Reefer, Amanda J., MS, Satinover, Shama M., MS, Solga, Michael D., MS, Lannigan, Joanne A., MS, Nguyen, Jennifer T., BS, Wilson, Barbara B., MD, Woodfolk, Judith A., MBChB, PhD
• Format: Journal Article
• Language: English
• Published: 2008
• Subjects: Allergy and Immunology; GITR; SCORAD; AD; T H2 cytokines; bacterial superantigen; allergen avoidance; SEB; Human regulatory T cells; APC; Atopic dermatitis; CLA; Antigen-presenting cell; Cutaneous lymphocyte-associated antigen; Staphylococcal enterotoxin B; CCR6; CD25; Glucocorticoid-induced TNF receptor–related protein; Foxp3; CCR4; SCORing Atopic Dermatitis
• DOI: 10.1016/j.jaci.2007.11.003
• ISSN: 0091-6749

Background It is unresolved whether circulating CD25hi CD4+ 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 (CD25neg CD4+ ). 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 TH 2 cytokines, and coculture with effector T cells selectively enhanced IL-5 production. Moreover, induction of a TH 2-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 TH 2 responses.