Early pediatric atopic dermatitis shows only a cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire CLA+ TH22/TC22 cell subsets

• Published in: Journal of allergy and clinical immunology Vol. 136; no. 4; pp. 941 - 951.e3
• Main Authors: Czarnowicki, Tali, Esaki, Hitokazu, Gonzalez, Juana, Malajian, Dana, Shemer, Avner, Noda, Shinji, Talasila, Sreya, Berry, Adam, Gray, Jayla, Becker, Lauren, Estrada, Yeriel, Xu, Hui, Zheng, Xiuzhong, Suárez-Fariñas, Mayte, Krueger, James G., Paller, Amy S., Guttman-Yassky, Emma
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2015; Elsevier Limited
• Subjects: Adolescent; Adult; Adults; Age; Aged; Antigens; Antigens, Differentiation, T-Lymphocyte - metabolism; Atopic dermatitis; Blood; CD69; Cell Separation; Child; Child, Preschool; cutaneous lymphocyte antigen; Cytokines; Dermatitis; Dermatitis, Atopic - immunology; Disease; Ethnicity; Flow Cytometry; HLA-DR; Humans; IFN-γ; IL-13; IL-22; Immunophenotyping; inducible costimulator; Infant; Interleukin-22; Interleukins - metabolism; Laboratories; Lymphocyte Activation; Lymphocytes; Membrane Glycoproteins - metabolism; Middle Aged; Studies; T cell; T cell receptors; T-Lymphocyte Subsets - immunology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Helper-Inducer - immunology; Th1-Th2 Balance; Young Adult; AD; PMA; T cell; IL-13; IL-22; TC; inducible costimulator; IFN-γ; HLA-DR; Atopic dermatitis; cutaneous lymphocyte antigen; PE; CLA; CD69; ICOS; TEM; TCM
• ISSN: 0091-6749; 1097-6825; 1097-6825
• DOI: 10.1016/j.jaci.2015.05.049

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. 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. 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 TH1/cytotoxic T (TC) 1, TH2/TC2, TH9/TC9, TH17/TC17, and TH22/TC22 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). Selective inducible costimulator activation (P < .001) was seen in children. CLA+ TH2 T cells were markedly expanded in both children and adults with AD compared with those in control subjects, but decreases in CLA+ TH1 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 TH22 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). These data suggest that TH2 activation within skin-homing T cells might drive AD in children and that reduced counterregulation by TH1 T cells might contribute to excess TH2 activation. TH22 “spreading” of AD is not seen in young children and might be influenced by immune development, disease chronicity, or recurrent skin infections.