Cumberbatch M, Dearman R J, Kimber I
Zeneca Central Toxicology Laboratory, Macclesfield, Cheshire, UK.
Immunology. 1997 Nov;92(3):388-95. doi: 10.1046/j.1365-2567.1997.00360.x.
The induction phase of contact sensitization is associated with the movement of epidermal Langerhans cells (LC) from the skin and their migration, via afferent lymphatics, to draining lymph nodes where they accumulate as immunostimulatory dendritic cells (DC). It has been demonstrated previously that tumour necrosis factor-alpha (TNF-alpha) provides an important signal for LC migration and that in the absence of this cytokine, movement of LC from the epidermis to regional lymph nodes is inhibited. Recent evidence indicates that interleukin-1 beta (IL-1 beta), a cytokine produced in murine epidermis exclusively by LC, may also play a role in LC migration. The purpose of the investigations described here was to clarify, using relevant neutralizing anti-cytokine antibodies, the contributions made by TNF-alpha and IL-1 beta to the migration of LC from the epidermis. It was found that like anti-TNF-alpha, anti-IL-1 beta administered systemically to mice (by intraperitoneal injection), prior to skin sensitization with the contact allergen oxazolone, resulted in a marked inhibition of DC accumulation in draining lymph nodes. It was shown also that anti-IL-1 beta inhibited TNF-alpha-induced LC migration and DC accumulation and that; in similar fashion, the stimulation of LC migration and DC accumulation induced by IL-1 beta was compromised by prior treatment with anti-TNF-alpha. Based upon these data it is proposed that the stimulation of LC migration in response to skin sensitization requires the receipt by LC of two independent signals, one provided by TNF-alpha and the other by IL-1 beta. Morphological analyses of LC in epidermal sheets prepared from animals exposed to these cytokines with or without prior systemic treatment with anti-cytokine antibody suggested that the changes induced in LC by TNF-alpha and IL-1 beta may include the altered expression of adhesion molecules and acquisition of the ability to interact with and pass through the basement membrane.
接触致敏的诱导阶段与表皮朗格汉斯细胞（LC）从皮肤的移动及其通过输入淋巴管迁移至引流淋巴结有关，在引流淋巴结中它们作为免疫刺激性树突状细胞（DC）聚集。先前已证明肿瘤坏死因子-α（TNF-α）为LC迁移提供重要信号，并且在缺乏这种细胞因子的情况下，LC从表皮向区域淋巴结的移动受到抑制。最近的证据表明，白细胞介素-1β（IL-1β），一种仅由LC在小鼠表皮中产生的细胞因子，也可能在LC迁移中起作用。本文所述研究的目的是使用相关的中和抗细胞因子抗体来阐明TNF-α和IL-1β对LC从表皮迁移的贡献。发现与抗TNF-α一样，在用接触性变应原恶唑酮对小鼠进行皮肤致敏之前，通过腹腔注射全身给予小鼠抗IL-1β，导致引流淋巴结中DC聚集受到明显抑制。还表明抗IL-1β抑制TNF-α诱导的LC迁移和DC聚集，并且；以类似方式，抗TNF-α预先处理会损害IL-1β诱导的LC迁移和DC聚集。基于这些数据，提出响应皮肤致敏对LC迁移的刺激需要LC接收两个独立信号，一个由TNF-α提供，另一个由IL-1β提供。对用或不用抗细胞因子抗体进行全身预处理后暴露于这些细胞因子的动物制备的表皮片中的LC进行形态学分析表明，TNF-α和IL-1β在LC中诱导的变化可能包括粘附分子表达的改变以及获得与基底膜相互作用并穿过基底膜的能力。
