Prevention of toxic epidermal necrolysis by regulatory T cells
Prevention of toxic epidermal necrolysis by regulatory T cells
复制标题
DOI：
10.1002/eji.200425773
复制
发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Itami, S
中科院分区：
文献类型：
--
作者：
Azukizawa, H;Sano, S;Itami, S
为了分析针对表皮皮肤抗原的自身反应性T细胞的免疫调节，我们将角蛋白5启动子(K5-MoVA)下的角质形成细胞选择性表达卵清蛋白的转基因小鼠(K5-MoVA)与表达K-b限制性OVA特异性T细胞受体转基因(OT-I)的小鼠进行杂交。在无瘤双转基因小鼠中，OT-I细胞在胸腺外发育，并在8-12周龄时开始严重的表皮损伤，类似于毒性表皮坏死松解(TEN)。相比之下，胸腺双转基因小鼠胸腺中的OT-I细胞缺失，外围几乎没有这种细胞，而且从未出现类似于TEN的皮肤变化。从胸腺双转基因小鼠分离的OT-I细胞过继转移在无胸腺K5-Mova单转基因小鼠中诱导的TEN。在无胸腺双转基因小鼠中，这种自发性疾病可以通过转移胸腺小鼠的淋巴细胞来预防，但当这些种群中的CD4(+)或CD25(+)细胞被耗尽时，这种自发性疾病并不能被预防。虽然纯化的CD4(+)CD25(+)细胞几乎不能预防过继转移OT-I细胞引起的皮肤病，但当与CD11c(+)树突状细胞共转移时，它们能有效地预防疾病。这些结果表明，胸腺来源的调节性T细胞与CD11c+树突状细胞协同作用，可预防威胁生命的皮肤损伤，如TEN。
To analyze immunoregulation of autoreactive T cells specific for epidermal skin antigens, we crossed transgenic mice expressing ovalbumin selectively in keratinocytes under the keratin 5 promoter (K5-mOVA) with mice expressing a K-b-restricted OVA-specific T cell receptor transgene (OT-I). In athymic double-transgenic mice, OT-I cells developed extrathymically and, at 8-12 weeks of age, initiated severe epidermal damage mimicking toxic epidermal necrolysis (TEN). In contrast, euthymic double-transgenic mice showed thymic deletion of OT-I cells, had few of these cells in the periphery, and never developed skin changes mimicking TEN. Adoptive transfer of OT-I cells isolated from euthymic double-transgenic mice induced TEN in athymic K5-mOVA single-transgenic mice. This spontaneous disease in athymic double-transgenic mice was prevented by transferring lymph node cells from euthymic mice, but was not prevented when CD4(+) or CD25(+) cells were depleted from this population. Although purified CD4(+)CD25(+) cells scarcely prevented the skin disease induced by adoptive transfer of OT-I cells, they efficiently prevented the disease when co-transferred with CD11c(+) dendritic cells. These results suggested that thymus-derived regulatory T cells cooperate with CD11c+ dendritic cells to prevent life-threatening skin damage such as TEN.