Department of Hematology, Oncology, and Pneumology, University Medical Center, Johannes Gutenberg University Mainz, 55131 Mainz, Germany.
J Immunol. 2011 Aug 1;187(3):1142-9. doi: 10.4049/jimmunol.1001491. Epub 2011 Jun 22.
Epidermal Langerhans cells (LC) are potent APCs surveying the skin. They are crucial regulators of T cell activation in the context of inflammatory skin disease and graft-versus-host disease (GVHD). In contrast to other dendritic cell subtypes, murine LC are able to reconstitute after local depletion without the need of peripheral blood-derived precursors. In this study, we introduce an experimental model of human skin grafted to NOD-SCID IL2Rγ(null) mice. In this model, we demonstrate that xenografting leads to the transient loss of LC from the human skin grafts. Despite the lack of a human hematopoietic system, human LC repopulated the xenografts 6 to 9 wk after transplantation. By staining of LC with the proliferation marker Ki67, we show that one third of the replenishing LC exhibit proliferative activity in vivo. We further used the skin xenograft as an in vivo model for human GVHD. HLA-disparate third-party T cells stimulated with skin donor-derived dendritic cells were injected intravenously into NOD-SCID IL2Rγ(null) mice that had been transplanted with human skin. The application of alloreactive T cells led to erythema and was associated with histological signs of GVHD limited to the transplanted human skin. The inflammation also led to the depletion of LC from the epidermis. In summary, we provide evidence that human LC are able to repopulate the skin independent of blood-derived precursor cells and that this at least partly relates to their proliferative capacity. Our data also propose xeno-transplantation of human skin as a model system for studying the role of skin dendritic cells in the efferent arm of GVHD.
表皮朗格汉斯细胞（LC）是一种强有力的抗原提呈细胞，可以检测皮肤。它们在炎症性皮肤病和移植物抗宿主病（GVHD）中是 T 细胞激活的关键调节者。与其他树突状细胞亚型不同，在没有外周血衍生前体的情况下，LC 可以在局部耗竭后重建。在这项研究中，我们引入了一种将人皮肤移植到 NOD-SCID IL2Rγ（null）小鼠的实验模型。在该模型中，我们证明异种移植会导致人皮肤移植物中 LC 的短暂丢失。尽管缺乏人类造血系统，但在移植后 6 至 9 周，人 LC 重新填充了异种移植物。通过用增殖标志物 Ki67 对 LC 进行染色，我们表明三分之一的补充 LC 在体内具有增殖活性。我们进一步将皮肤异种移植作为体内人 GVHD 的模型。用皮肤供体来源的树突状细胞刺激 HLA 不同的第三方 T 细胞，然后静脉内注射到已移植人皮肤的 NOD-SCID IL2Rγ（null）小鼠中。同种反应性 T 细胞的应用导致红斑，并伴有仅局限于移植人皮肤的 GVHD 的组织学迹象。炎症还导致表皮 LC 的耗竭。总之，我们提供的证据表明，LC 能够独立于血液衍生前体细胞来填充皮肤，这至少部分与它们的增殖能力有关。我们的数据还提出了异种移植人皮肤作为研究 GVHD 传出臂中皮肤树突状细胞作用的模型系统。
