Biology of Langerhans cells: selective migration of Langerhans cells into allogeneic and xenogeneic grafts on nude mice

Abstract

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.