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

Abstract

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 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).

Results: 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).

Conclusions: 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.

Keywords: Atopic dermatitis; CD69; HLA-DR; IFN-γ; IL-13; IL-22; T cell; cutaneous lymphocyte antigen; inducible costimulator.

Conflict of interest statement

Disclosures: The authors have declared that they have no conflict of interest.

Copyright © 2015 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1. CD4 and CD8 T-cell subsets in children and adults with AD vs. controls

A–B) Naïve T-cell frequency was higher in both control and AD children compared to adults, while Tcm/Tem subsets were lower in control and AD children than adults. Adults with AD had significantly higher effector cells compared with AD children.

Figure 2. ICOS expression in CLA+ and CLA− memory T-cell subsets in adult and pediatric AD

A) AD patients had increased ICOS expression in both CLA+ and CLA− memory subsets compared to their relative controls. No significant CD4 ICOS expression differences were observed between the AD groups in both CLA+/CLA− Tem/Tcm. B) Contrary to adults, in which higher CD8 ICOS expression was measured in CLA+ Tcm/Tem cells compared to their relative controls, no differences were observed between AD children and controls.

Figure 3. HLA-DR expression in in CLA+ and CLA− memory T-cell subsets in adult and pediatric AD

A) Comparable levels of HLA-DR expression on Tcm/Tem cells between children with and without AD. B) AD adults had higher HLA-DR expression compared to controls, particularly among the CLA+ and CD8 populations. C) Lower CD69 in adults than in children with AD in both CD4 and CD8 subsets.

Figure 4. IFN-γ and IL-13 polarization in CLA+ and CLA− CD4 and CD8 T-cells

A) Compared to children, adults with AD had significantly higher levels of IFN-γ, particularly in CD4 T-cells. IFN-γ+CLA+ in AD children was significantly lower than control children. B) In adults IL-13 was higher in the AD group compared to controls in both CLA+/CLA− CD4/CD8 subsets. In children this difference was most prominent among CD4 CLA+ T-cells. C) AD children had markedly lower Th1:Th2 ratio compared with controls, particularly in CD4 CLA+ cells.

Figure 5. IL-22, IL-17 and IL-9 frequency in CLA+ and CLA− CD4 and CD8 T-cells

A) No significant IL-22 differences were measured between children with and without AD. B) Th17/Tc17 levels were higher in AD adults versus children, specifically in the CLA− CD4/CD8 subsets. C) AD adults had higher Th9 levels in CLA+ cells than AD children.