Course of Integrated Medicine, Department of Dermatology, Osaka University, Graduate School of Medicine, Osaka, Japan.
J Dermatol. 2011 Mar;38(3):255-60. doi: 10.1111/j.1346-8138.2010.01173.x.
Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe acute exfoliative skin diseases developing extensive epidermal detachment and mucosal damage. Although SJS and TEN are mostly caused by drugs, an animal model of TEN using drugs has not been established yet. We have established an autoimmune skin disease model mouse reproducing the devastating skin damage of TEN by a combination of transgenic mice expressing an epidermal model antigen and its specific CD8(+) T-cell receptor. In this model mouse, we found that the thymus-derived CD4(+) CD25(+) regulatory T cell (Treg) is a critical regulator of cytotoxic T lymphocytes (CTL) causing TEN. Indeed, loss of Treg function was recently demonstrated by human studies of TEN patients. Although how drug-reactive CTL is activated in vivo is still unknown, this model elucidated the immunological pathomechanism of TEN after CTL obtained cytotoxicity against epidermal keratinocyte. In this review, roles of CTL, Treg, cytotoxic granules and antigen-presenting cells were discussed on pathogenesis of TEN.
史蒂文斯-约翰逊综合征（SJS）和中毒性表皮坏死松解症（TEN）是严重的急性剥脱性皮肤疾病，会导致广泛的表皮脱落和黏膜损伤。尽管 SJS 和 TEN 主要由药物引起，但尚未建立使用药物的 TEN 动物模型。我们通过表达表皮模型抗原及其特异性 CD8(+) T 细胞受体的转基因小鼠组合，建立了一种可重现 TEN 严重皮肤损伤的自身免疫性皮肤病模型小鼠。在这种模型小鼠中，我们发现胸腺来源的 CD4(+) CD25(+) 调节性 T 细胞（Treg）是导致 TEN 的细胞毒性 T 淋巴细胞（CTL）的关键调节因子。事实上，TEN 患者的人类研究最近证明了 Treg 功能的丧失。尽管体内药物反应性 CTL 是如何被激活的仍不清楚，但该模型阐明了 CTL 对表皮角质形成细胞获得细胞毒性后 TEN 的免疫发病机制。在这篇综述中，讨论了 CTL、Treg、细胞毒性颗粒和抗原呈递细胞在 TEN 发病机制中的作用。
