Teraki Yuichi, Shiohara Tetsuo
Department of Dermatology, Kyorin University School of Medicine, 6-20-2 Shinkawa, Mitaka, Tokyo 181-8611, Japan.
J Allergy Clin Immunol. 2003 Sep;112(3):609-15. doi: 10.1016/s0091-6749(03)01624-5.
Although effector and regulatory T cells play roles in the progression and resolution of inflammatory diseases, respectively, little in vivo data exist regarding the T-cell dynamics in the pathogenesis of inflammatory skin diseases in humans.
Our aim is to phenotypically and functionally characterize the T cells responsible for initiation and regulation of inflammatory events in fixed drug eruption (FDE) as a disease model to study the role of cytokines produced within the epidermis in the pathogenesis of inflammatory skin disease.
By use of flow cytometry, we phenotypically and functionally characterized the intraepidermal T cells that persist as a stable population in resting (pigmented) FDE lesions and that are present in active FDE lesions.
In resting FDE lesions, most of the intraepidermal T cells were of the CD8 phenotype, most of which expressed cutaneous lymphocyte-associated antigen, alpha4beta1, CD11a, alphaEbeta7, and CD45RA but not CD27, CD62L, CCR4, or CCR7. This population selectively expressed CD122 but not CD25. Intracellular staining demonstrated that most intraepidermal CD8+ T cells were capable of producing IFN-gamma and TNF-alpha but produced little IL-2 and IL-4. On the other hand, in the FDE lesions that arose after challenge, a significant number of CD4+ T cells capable of producing IL-10 migrated into the lesional epidermis. Moreover, nearly 70% of the CD4+ T cells migrating into the lesional epidermis expressed CD25.
Effector IFN-gamma-producing CD8+ T cells and regulatory IL-10-producing CD4+ T cells might be responsible for the progression and resolution of FDE, respectively.
尽管效应性T细胞和调节性T细胞分别在炎症性疾病的进展和消退中发挥作用,但关于人类炎症性皮肤病发病机制中T细胞动力学的体内数据很少。
我们的目的是对固定性药疹(FDE)中负责启动和调节炎症事件的T细胞进行表型和功能特征分析,FDE作为一种疾病模型,用于研究表皮内产生的细胞因子在炎症性皮肤病发病机制中的作用。
通过流式细胞术,我们对静止期(色素沉着)FDE皮损中作为稳定群体持续存在以及活动期FDE皮损中存在的表皮内T细胞进行了表型和功能特征分析。
在静止期FDE皮损中,大多数表皮内T细胞为CD8表型,其中大多数表达皮肤淋巴细胞相关抗原、α4β1、CD11a、αEβ7和CD45RA,但不表达CD27、CD62L、CCR4或CCR7。这群细胞选择性表达CD122但不表达CD25。细胞内染色显示,大多数表皮内CD8+ T细胞能够产生IFN-γ和TNF-α,但产生的IL-2和IL-4很少。另一方面,在激发后出现的FDE皮损中,大量能够产生IL-10的CD4+ T细胞迁移到皮损表皮。此外,迁移到皮损表皮的CD4+ T细胞中近70%表达CD25。
产生效应性IFN-γ的CD8+ T细胞和产生调节性IL-10的CD4+ T细胞可能分别负责FDE的进展和消退。