Mizukawa Yoshiko, Takahashi Ryo, Yamazaki Yoshimi, Kimishima Momoko, Shiohara Tetsuo
Department of Dermatology, Kyorin University School of Medicine, Tokyo, Japan.
Exp Dermatol. 2008 Mar;17(3):170-6. doi: 10.1111/j.1600-0625.2007.00656.x. Epub 2007 Dec 7.
Patients with atopic dermatitis (AD) have an abnormally increased frequency of cutaneous lymphocyte antigen (CLA)+ Th2 cells responsible for local inflammation; however, this is paradoxical, given the well-recognized defective capacity of Th2 cells to migrate to the skin sites of inflammation. These discrepant observations would stem from the ambiguity of CLA+ T cells, because CLA does not represent the epitope required for binding to E-selectin but the epitope generated by fucosyltransferase VII (Fuc-TVII) and because skin-homing T cells are composed of three distinct subpopulations; Fuc-TVII+ E-selectin ligand (ESL)+ CLA-, Fuc-TVII+ ESL+ CLA+ and Fuc-TVII- ESL- CLA+ cells. We therefore asked which subpopulations of skin-homing Th2 cells could be increased in the blood and skin lesions of AD. We analysed the frequencies of the three subpopulations in purified CD4+ peripheral blood T cells from AD patients and healthy controls by immunohistochemistry and flow cytometry. The Fuc-TVII+ CLA+ or CLA+ ESL+ CCR4+ cells were dramatically increased in frequency not only in the blood but also in the skin lesions of AD patients and this increase was related to the severity of the clinical symptoms. Our data indicate the clinical importance of identifying skin-homing T cells with the potent capacity to migrate into the skin by analysing their Fuc-TVII expression and E-selectin binding ability in patients with AD.
特应性皮炎(AD)患者中,负责局部炎症的皮肤淋巴细胞抗原(CLA)+ Th2细胞频率异常增加;然而,鉴于Th2细胞迁移至炎症皮肤部位的能力公认存在缺陷,这一现象显得自相矛盾。这些相互矛盾的观察结果源于CLA+ T细胞的模糊性,因为CLA并不代表与E-选择素结合所需的表位,而是由岩藻糖基转移酶VII(Fuc-TVII)产生的表位,并且皮肤归巢T细胞由三个不同的亚群组成;Fuc-TVII+ E-选择素配体(ESL)+ CLA-、Fuc-TVII+ ESL+ CLA+和Fuc-TVII- ESL- CLA+细胞。因此,我们探究了在AD患者的血液和皮肤病变中,哪些皮肤归巢Th2细胞亚群会增加。我们通过免疫组织化学和流式细胞术分析了AD患者和健康对照者纯化的CD4+外周血T细胞中这三个亚群的频率。Fuc-TVII+ CLA+或CLA+ ESL+ CCR4+细胞不仅在AD患者的血液中,而且在其皮肤病变中的频率都显著增加,并且这种增加与临床症状的严重程度相关。我们的数据表明,通过分析AD患者中皮肤归巢T细胞的Fuc-TVII表达和E-选择素结合能力,来识别具有强大迁移至皮肤能力的皮肤归巢T细胞具有临床重要性。