Laboratory for Investigative Dermatology, Rockefeller University, New York, NY.
Translational Technology Core Laboratory, Rockefeller University, New York, NY.
J Allergy Clin Immunol. 2015 Jul;136(1):104-115.e7. doi: 10.1016/j.jaci.2015.01.020. Epub 2015 Mar 3.
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 TH9, TH17, and TH22 T-cell populations in human subjects.
We sought to quantify TH1, TH2, TH9, TH17, and TH22 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.
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-γ-, IL-22-, IL-13-, IL-17-, and IL-9-producing CD4(+) and CD8(+) T cells were compared in CLA(-) and CLA(+) populations.
We measured increased TH2/TC2/IL-13(+) and TH22/TC22/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-γ-producing cells was observed in patients with AD, with no significant differences in CLA(-) T-cell numbers. The CLA(+) TH1/TH2 and TC1/TC2 ratio was highly imbalanced in patients with AD (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).
Severe AD is accompanied by expansion of skin-homing TH2/TC2 and TH22/TC22 subsets with lower TH1/TC1 frequencies. These data create a critical basis for studying alterations in immune activation in adults and pediatric patients with AD.
过去对特应性皮炎（AD）患者血液 T 细胞表型的研究结果存在争议，且大多是在人类 TH9、TH17 和 TH22 T 细胞群被鉴定之前进行的。
我们旨在定量检测 AD 患者和对照者的皮肤淋巴细胞抗原（CLA）阳性和 CLA 阴性 T 细胞亚群中的 TH1、TH2、TH9、TH17 和 TH22 T 细胞群及其相应的 CD8+T 细胞亚群。
我们使用 11 色流式细胞术抗体面板研究了 42 名重度 AD 患者（平均 SCORAD 评分 65）和 25 名健康对照者。比较了 CLA(-)和 CLA(+)群体中 IFN-γ、IL-22、IL-13、IL-17 和 IL-9 产生的 CD4+和 CD8+T 细胞的频率。
与对照组相比，严重 AD 患者的 TH2/TC2/IL-13(+)和 TH22/TC22/IL-22(+)群体增加（P <.1），CLA(+)T 细胞数量存在显著差异（P <.01）。AD 患者的 CLA(+)IFN-γ产生细胞频率显著降低，而 CLA(-)T 细胞数量无显著差异。AD 患者的 CLA(+)TH1/TH2 和 TC1/TC2 比值严重失衡（分别为 10 对 3 [P =.005]和 19 对 7 [P <.001]）。IL-13 和 IL-22 产生的 CD4+和 CD8+T 细胞频率之间存在正相关（r 值分别为 0.5 和 0.8，P <.0001），并且 CLA(+)细胞产生的 IL-13 水平与 IgE 水平和 SCORAD 评分相关。患有皮肤感染的 AD 患者的 CD4+IL-22(+)和 IL-17(+)细胞频率较高，在 CLA(-)细胞中差异具有统计学意义（IL-22：3.7 对 1.7 [P <.001]和 IL-17：1.7 对 0.6 [P <.001]），而在 CLA(+)T 细胞中差异较小（IL-22：11 对 7.5，P =.04）。
严重 AD 伴有皮肤归巢 TH2/TC2 和 TH22/TC22 亚群的扩增，TH1/TC1 频率降低。这些数据为研究 AD 成人和儿科患者免疫激活的改变提供了重要依据。
