The role of dendritic cells in the etiology of atopic dermatitis -analysis using mouse model

用OX或TNCB溶液致敏BALB/c小鼠，然后在原始致敏部位用相同的抗原反复诱导。半抗原特异性的耳肿胀反应从迟发性超敏反应转变为早期的晚期反应。将小鼠分为两组。采用流式细胞术检测急性期和慢性期小鼠淋巴CD11c+DC经脂多糖刺激后IL-1和肿瘤坏死因子-α的产生。慢性期与活动期相比，两种细胞因子的产生均明显减少。提示慢性期CD11c~+DC数量减少。我们从慢性期淋巴结细胞中去除DC，然后加入从急性期淋巴结细胞中获得的DC。结果，CD8+T细胞产生的干扰素-γ增加。随后，我们将从慢性期淋巴结细胞中获得的DC加入到急性期淋巴结细胞中，从急性期淋巴结细胞中去除了DC。显著抑制CD8+T细胞产生干扰素-γ。这些结果提示，DC分泌的细胞因子的减少可能在慢性期淋巴结细胞Th1应答的抑制和Th1向Th2的转化中起重要作用。免疫组织化学检测显示，慢性期皮肤CD11c+DC的数量低于急性期。这一结果与在淋巴结细胞中观察到的结果一致。综合这些结果，这些结果表明在慢性期皮肤和淋巴结节中。CD11c^+DC进入激活诱导的细胞死亡，导致Th1反应被抑制。

BALB/c mice were sensitized by the application of OX or TNCB solutions to the ear, then were repeatedly elicited on the original sensitized site with the same antigen. Hapten-specific ear swelling reaction was shifted from delayed hypersensitivity to early-type of the late phase reaction. Mice were divided into two groups. One group was elicited only once (acute phase), while the other group was repeatedly elicited during 24 days (chronic phase).We measured LPS-stimulated IL-1 and TNF-α production from lymphnode CD11c ^+DC obtained from acute phase or chronic phase mice, using flowcytometry. Production of both cytokines was remarkably reduced in chronic phase in comparison with acte phase. This result indicates that the number of CD11c ^+DC was reduced in chronic phase. We eliminated DC from chronic phase lymphnode cells, then added DC obtained from acute phase lymphnode cells. As a result, IFN-γ production from CD8 ^+T cells increased. Subsequently we added DC obtained from chronic phase lymphnode cells to acute phase lymphnode cells, from which DC had been eliminated. It resulted in prominent suppression of IFN-γ production from CD8 ^+T cells. These results suggest that reduction of cytokine production from DC may play an important role for inhibition of Th1 response and shift from a Th1 to a Th2 response in chronic phase lymphnode cells.Immunohistological examination revealed the number of CD11c ^+DC was reduced in chronic phase skin in comparison with acute phase one. This result is consistent with one observed in lymphnode cells.Taken together, these results indicate that in chronic phase skin and lymphnode. CD11c ^+DC fall into activation-induced cell death, leading to suppression of a Th1 response.