Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)⁺ T_H2/T_H1 cell imbalance, whereas adults acquire CLA⁺ T_H22/T_C22 cell subsets

Background Identifying differences and similarities between cutaneous lymphocyte antigen (CLA)⁺ polarized T-cell subsets in children versus adults with atopic dermatitis (AD) is critical for directing new treatments toward children. Objective We sought to compare activation markers and frequencies of skin-homing (CLA⁺) versus systemic (CLA^-) "polar" CD4 and CD8 T-cell subsets in patients with early pediatric AD, adults with AD, and control subjects. Methods Flow cytometry was used to measure CD69/inducible costimulator/HLA-DR frequency in memory cell subsets, as well as IFN-γ, IL-13, IL-9, IL-17, and IL-22 cytokines, defining T_H1/cytotoxic T (T_C) 1, T_H2/T_C2, T_H9/T_C9, T_H17/T_C17, and T_H22/T_C22 populations in CD4 and CD8 cells, respectively. We compared peripheral blood from 19 children less than 5 years old and 42 adults with well-characterized moderate-to-severe AD, as well as age-matched control subjects (17 children and 25 adults). Results Selective inducible costimulator activation (P <.001) was seen in children. CLA⁺ T_H2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA⁺ T_H1 T-cell numbers were greater in children with AD (17% vs 7.4%, P =.007). Unlike in adults, no imbalances were detected in CLA^- T cells from pediatric patients with AD nor were there altered frequencies of T_H22 T cells within the CLA⁺ or CLA^- compartments. Adults with AD had increased frequencies of IL-22-producing CD4 and CD8 T cells within the skin-homing population, compared with controls (9.5% vs 4.5% and 8.6% vs 2.4%, respectively; P <.001), as well as increased HLA-DR activation (P <.01). Conclusions These data suggest that T_H2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by T_H1 T cells might contribute to excess T_H2 activation. T_H22 "spreading" of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.