Severe atopic dermatitis is characterized by selective expansion of circulating TH2/TC2 and TH22/TC22, but not TH17/TC17, cells within the skin-homing T-cell population

Background: Past studies of blood T-cell phenotyping in patients with atopic dermatitis (AD) have provided controversial results and were mostly performed before the identification of T(H)9, T(H)17, and T(H)22 T-cell populations in human subjects. Objective: We sought to quantify T(H)1, T(H)2, T(H)9, T(H)17, and T(H)22 T-cell populations and corresponding CD8(+) T-cell subsets in both cutaneous lymphocyte antigen (CLA)-positive and CLA(-) T-cell subsets in patients with AD and control subjects. Methods: We studied 42 adults with severe AD (mean SCORAD score, 65) and 25 healthy subjects using an 11-color flow cytometric antibody panel. Frequencies of IFN-gamma-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations. Results: We measured increased T(H)2/T(C)2/IL-13(+) and T(H)22/T(C)22/IL-22(+) populations (P <.1) in patients with severe AD versus control subjects, with significant differences in CLA(+) T-cell numbers (P <.01). A significantly lower frequency of CLA(+) IFN-gamma-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) T(H)1/T(H)2 and T(C)1/T(C)2 ratio was highly imbalanced in patients withAD (10 vs 3 [P = .005] and 19 vs 7 [P < .001], respectively). Positive correlations were found between frequencies of IL-13- and IL-22- producing CD4(+) and CD8(+) T cells (r = 0.5 and 0.8, respectively; P < .0001), and frequencies of IL-13-producing CLA(+) cells were also correlated with IgE levels and SCORAD scores. Patients with AD with skin infections had higher CD4(+) IL-22(+) and IL-17(+) cell frequencies, which were highly significant among CLA(-) cells (IL-22: 3.7 vs 1.7 [P < .001] and IL-17: 1.7 vs 0.6 [P < .001]), with less significant effects among CLA(+) T cells (IL-22: 11 vs 7.5, P = .04). Conclusions: Severe AD is accompanied by expansion of skinhoming T(H)2/T(C)2 and T(H)22/T(C)22 subsets with lower T(H)1/T(C)1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.