Reefer Amanda J, Satinover Shama M, Solga Michael D, Lannigan Joanne A, Nguyen Jennifer T, Wilson Barbara B, Woodfolk Judith A
Asthma and Allergic Diseases Center, University of Virginia Health System, Charlottesville, VA 22908-1355, USA.
J Allergy Clin Immunol. 2008 Feb;121(2):415-422.e3. doi: 10.1016/j.jaci.2007.11.003. Epub 2008 Jan 4.
It is unresolved whether circulating CD25hiCD4+ T cells in patients with atopic dermatitis who have elevated IgE (IgE(high)) are regulatory or effector in nature.
To analyze the properties of CD25hi T-cell subtypes in IgE(high) atopic dermatitis.
The phenotype of circulating CD25hi T cells was analyzed by flow cytometry using PBMCs from patients with atopic dermatitis (total IgE > 250 IU/mL). Cytokines induced in CD25hi subtypes were analyzed after activation with anti-CD3 mAb (+/-IL-2) and in the presence of activated autologous effector T cells (CD25negCD4+). Reactivity to bacterial superantigen derived from the skin-colonizing organism Staphylococcus aureus was also evaluated.
CD25(hi) T cells expressing regulatory T-cell markers (Foxp3, CCR4, cutaneous lymphocyte-associated antigen) were increased in atopic dermatitis compared with IgE(low) controls. This phenomenon was linked to disease severity. Two subtypes of CD25hi T cells were identified on the basis of differential expression of the chemokine receptor CCR6. Although the ratio of CCR6+ and CCR6neg subtypes within the CD25hi subset was unaltered in atopic dermatitis, each subtype proliferated spontaneously ex vivo, suggesting in vivo activation. Activated CCR6neg cells secreted T(H)2 cytokines, and coculture with effector T cells selectively enhanced IL-5 production. Moreover, induction of a T(H)2-dominated cytokine profile on activation with bacterial superantigen was restricted to the CCR6neg subtype.
Despite a regulatory phenotype, activated CD25hi T cells that lack expression of CCR6 promote T(H)2 responses.
在IgE升高（IgE(high)）的特应性皮炎患者中，循环CD25hiCD4+ T细胞本质上是调节性的还是效应性的尚未明确。
分析IgE(high)特应性皮炎中CD25hi T细胞亚群的特性。
使用来自特应性皮炎患者（总IgE > 250 IU/mL）的外周血单核细胞，通过流式细胞术分析循环CD25hi T细胞的表型。在用抗CD3单克隆抗体（±IL-2）激活后，以及在存在活化的自体效应T细胞（CD25negCD4+）的情况下，分析CD25hi亚群中诱导产生的细胞因子。还评估了对源自皮肤定植菌金黄色葡萄球菌的细菌超抗原的反应性。
与IgE(low)对照组相比，特应性皮炎患者中表达调节性T细胞标志物（Foxp3、CCR4、皮肤淋巴细胞相关抗原）的CD25(hi) T细胞增加。这种现象与疾病严重程度相关。根据趋化因子受体CCR6的差异表达，鉴定出CD25hi T细胞的两种亚群。尽管在特应性皮炎中CD25hi亚群内CCR6+和CCRneg亚群的比例未改变，但每个亚群在体外均自发增殖，提示体内活化。活化的CCRneg细胞分泌TH2细胞因子，与效应T细胞共培养可选择性增强IL-5的产生。此外，用细菌超抗原激活后诱导的以TH2为主的细胞因子谱仅限于CCRneg亚群。
尽管具有调节性表型，但缺乏CCR6表达的活化CD25hi T细胞可促进TH2反应。
