Hoefakker S, Balk H P, Boersma W J, van Joost T, Notten W R, Claassen E
Division of Immunological and Infectious Diseases, TNO Prevention and Health, Leiden, The Netherlands.
Immunology. 1995 Oct;86(2):296-303.
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-1 alpha (IL-1 alpha), IL-1 beta and tumour necrosis factor-alpha (TNF-alpha), 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.
荧光接触性化学变应原在应用于小鼠的同基因和异基因皮肤移植后可引发致敏。我们试图确定人皮肤移植的接触致敏反应中的功能活性在抗原摄取和迁移水平是否受到影响。在异种皮肤移植后，我们检测了移植皮肤局部暴露于异硫氰酸罗丹明B（RITC）的效果。本文描述了携带RITC的细胞和人类主要组织相容性复合体（MHC）II类DR（HLA - DR）+细胞从移植皮肤迁移至小鼠引流淋巴结的过程。免疫组织化学显示，移植导致移植皮肤内人HLA - DR+和CD1a+细胞随时间减少，而小鼠MHC II类（Ia）+细胞增加。与6周龄或9周龄的移植皮肤相比，在3周龄的人皮肤移植上应用RITC显示出最佳的迁移能力。此外，引流淋巴结中RITC+和HLA - DR+细胞频率随时间增加，以及3周龄人皮肤移植中HLA - DR+细胞随时间减少是同时发生的。原位分析人细胞因子白细胞介素 - 1α（IL - 1α）、IL - 1β和肿瘤坏死因子 - α（TNF - α）支持了这些数据，表明角质形成细胞产生细胞因子（一种与树突状细胞迁移相关的特性）在人皮肤移植中得以保留。因此，如同同种异体移植皮肤接触致敏中的树突状细胞一样，人异种移植到裸鼠皮肤上的树突状细胞在应用变应原后能够迁移至小鼠引流淋巴结。在人皮肤移植到裸鼠的模型中诱导接触性超敏反应是可能的，尽管使用这种体外模型分析接触敏感性可能仅限于移植后3周。
