Transfer of human leukocytes into double-knockout Pfp-/-Rag2-/- mice grafted with human skin: increased accumulation of neutrophils in human dermal microvessels

Severe combined immunodeficient mice reconstituted with human leukocytes have been useful to model parts of the human immune system, including some of its diseases (e.g., AIDS). Because no human polymorphonuclear leukocytes (huPMN) develop in these xenograft models, diseases such as several forms of vasculitis cannot be modeled using this approach. To provide such a model for vasculitis, human skin patches were grafted onto double-knockout Pfp(-/-)Rag2(-/-) mice, which not only lack functional T and B cells but which are also devoid of natural killer cells. After intravenous injection, a high proportion of huPMNs survived within the circulation and accumulated in the human blood vessels. The accumulation increased considerably after the endothelium of the skin patches had been stimulated by tumor necrosis factor-alpha. Alpha mild perivascular neutrophilic infiltration and vascular necrosis was observed in the microvessels of the skin patches. Thus, a xenograft model of vasculitis with predominant huPMNs infiltration has been established for the first time.