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Migration of human antigen-presenting cells in a human skin graft onto nude mice model after contact sensitization

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Author: Hoefakker, S. · Balk, H.P. · Boersma, W.J.A. · Joost, T. van · Notten, W.R.F. · Claassen, E.
Institution: TNO Preventie en Gezondheid
Source:Immunology, 2, 86, 296-303
Identifier: 232918
Keywords: Biology · Contact allergen · HLA DR antigen · Interleukin 1alpha · Interleukin 1beta · Rhodamine b · Tumor necrosis factor alpha · Adult · Animal experiment · Animal model · Antigen presenting cell · Cell migration · Controlled study · Dendritic cell · Immunohistochemistry · Keratinocyte · Lymph node · Mouse · Nonhuman · skin transplantation · Xenograft · Adult · Animal · Cell Movement · Cytokines · Dendritic Cells · Dermatitis, Contact · Epidermis · Female · Human · Immunoenzyme Techniques · Lymph Nodes · Mice · Mice, Inbred BALB C · Skin Transplantation · Time Factors · Transplantation, Heterologous


Fluorescent contact chemical allergens provoke sensitization after application on both syngeneic and allogeneic skin grafts in mice. We attempted to determine whether the functional activity in a contact sensitization response of human skin graft was affected at the level of antigen uptake and migration. After xenogeneic skin transplantation, we examined the effect of topical exposure of the graft to rhodamine B isothiocyanate (RITC). This paper describes the migration of RITC-carrying cells and human major histocompatibility complex (MHC) class II DR (HLA-DR)+ cells, from the graft to mouse draining lymph nodes. As demonstrated by immunohistochemistry, grafting resulted in a time-dependent decrease of human HLA-DR+ and CD1a+ cells, and an increase of mouse MHC class II (Ia)+ cells within the graft. Application of RITC on a 3-week-old human skin graft showed optimal migration capability compared to 6- or 9-week-old grafts. In addition, the time-dependent increase of frequencies of RITC+ and HLA-DR+ cells in the draining lymph nodes, and the time-dependent decrease of HLA-DR+ cells in the 3-week-old human skin graft, were concurrent. Supporting these data, human cytokine interleukin-1α (IL-1α), IL-1β and tumour necrosis factor-α (TNF-α), analysis in situ revealed that cytokine production by keratinocytes, a property associated with dendritic cell migration, was preserved in the human skin graft. Thus, like dendritic cells in contact sensitization in allografted skin, dendritic cells from human xenografted skin onto nude mice are capable of migration to mouse draining lymph nodes after allergen application. Induction of contact hypersensitivity is possible in a human skin graft onto nude mice model, although the use of this ex vivo model to analyze contact sensitivity is probably limited to 3 weeks after transplantation. Chemicals/CAS: rhodamine B, 81-88-9; Cytokines