Krueger G G, Daynes R A, Emam M
Proc Natl Acad Sci U S A. 1983 Mar;80(6):1650-4. doi: 10.1073/pnas.80.6.1650.
A major question challenging immunobiologists relates to those mechanisms that control the selective movement of cells involved in immune and inflammatory processes at various tissue sites such as the skin. Little is known about those influences that control the selective migration of macrophage-like Langerhans cells (LC) to normal epidermis, where it is uniformly distributed. Mechanistically, this includes the interaction of blood-borne LC precursors with the vascular endothelium of the skin and those factors that control the migration of the LC into the avascular epidermal component of the skin. By using (i) monoclonal antibodies specific for I-region associated Ia antigens found on LC from various inbred strains of animals and (ii) the congenitally athymic (nude) mouse as an immunologically compromised recipient of allografts and selected xenografts, we developed a model system to study the factors that restrict LC migration into the epidermis. Using this model, which excludes the need to lethally x-irradiate graft recipients, we established that: (i) the ingress of LC does not show major histocompatibility complex restriction [LC of the nude host are capable of migrating into the epidermis of allogeneic and certain xenogeneic (rat) skin grafts]; (ii) host LC are incapable of migrating into the epidermis of guinea pig or human skin grafts; (iii) the ingress of host LC into the epidermis of the graft is not accompanied by an overgrowth of the graft by host epidermis; and (iv) LC or LC precursors are capable of dividing in the skin or, alternatively, represent an extremely long-lived cell population. The specificity of this model system provides a powerful tool to help understand many aspects of LC biology. Grafting human skin to the nude mouse not only provides a biologic support system for the graft but also is, by design, a system that is devoid of contaminating circulating precursor cell types. Manipulation of the experimental conditions is quite easy and provides a highly specific means to investigate many parameters of LC function.
免疫生物学家面临的一个主要问题涉及控制参与免疫和炎症过程的细胞在皮肤等各种组织部位进行选择性移动的机制。对于控制巨噬细胞样朗格汉斯细胞（LC）向正常表皮选择性迁移的影响因素，人们了解甚少，而LC在正常表皮中呈均匀分布。从机制上讲，这包括血源性LC前体细胞与皮肤血管内皮的相互作用，以及控制LC迁移到皮肤无血管表皮成分中的那些因素。通过使用（i）针对在各种近交系动物的LC上发现的I区相关Ia抗原的单克隆抗体，以及（ii）先天性无胸腺（裸）小鼠作为同种异体移植物和选定异种移植物的免疫受损受体，我们开发了一个模型系统来研究限制LC迁移到表皮中的因素。使用这个无需对移植物受体进行致死性X射线照射的模型，我们确定：（i）LC的进入不显示主要组织相容性复合体限制[裸宿主的LC能够迁移到同种异体和某些异种（大鼠）皮肤移植物的表皮中]；（ii）宿主LC无法迁移到豚鼠或人类皮肤移植物的表皮中；（iii）宿主LC进入移植物表皮并不伴随着宿主表皮使移植物过度生长；以及（iv）LC或LC前体细胞能够在皮肤中分裂，或者代表一个寿命极长的细胞群体。这个模型系统的特异性为帮助理解LC生物学的许多方面提供了一个强大的工具。将人类皮肤移植到裸鼠身上不仅为移植物提供了一个生物支持系统，而且从设计上来说，也是一个没有循环前体细胞类型污染的系统。实验条件的操作相当容易，为研究LC功能的许多参数提供了一种高度特异性的手段。
