Auffermann-Gretzinger Susanne, Eger Lars, Bornhäuser Martin, Schäkel Knut, Oelschlaegel Uta, Schaich Markus, Illmer Thomas, Thiede Christian, Ehninger Gerhard
Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus der Technischen Universität, Fetscherstrasse 74, D-01307 Dresden, Germany.
Transplantation. 2006 Mar 27;81(6):866-73. doi: 10.1097/01.tp.0000203318.16224.57.
Both number and origin (donor vs. host) of dendritic cells (DC) are associated with acute graft-versus-host disease (aGvHD), relapse and graft failure after human allogeneic hematopoietic cell transplantation (aHCT).
We prospectively and simultaneously investigated skin and blood DC subtypes, their donor/recipient origin, and the correlation of DC reconstitution kinetics with treatment, clinical outcome, and incidence of aGvHD in patients undergoing aHCT.
A significant reduction of skin and a marked decrease of blood DC were observed in patients compared to healthy volunteers. A dominant donor chimerism of migratory Langerhans cells (LC) and dermal-dendritic-cells (DDC) was detected even early after transplantation, and developed independently from chemotherapy regimen, graft manipulation or time point after transplantation. Before start of the therapy patients showed significantly decreased numbers of peripheral blood CD123+ preDC2, whereas CD11c+ preDC1 numbers appeared to be diminished, but were statistically indistinguishable from controls. Host derived pB preDC were virtually absent following aHCT. After a further reduction in cell number around day 56 both preDC subtypes reconstituted and stabilized to pretransplant numbers by day 112. Occurrence of aGvHD and its treatment diminished numbers of both preDC subtypes. Furthermore conditioning therapy with Alemtuzumab apparently affected reconstitution of both preDC subsets negatively.
Given that induction of GvHD in humans is as host DC dependent as in mouse models, investigation of DC chimerism and number at different sites and especially in GvHD target organs might provide important insights into the pathogenesis of the main obstacle of aHCT.
树突状细胞（DC）的数量和来源（供体与宿主）均与人类异基因造血细胞移植（aHCT）后的急性移植物抗宿主病（aGvHD）、复发及移植物失败相关。
我们前瞻性地同时研究了接受aHCT患者的皮肤和血液DC亚群、其供体/受体来源，以及DC重建动力学与治疗、临床结局和aGvHD发生率之间的相关性。
与健康志愿者相比，患者的皮肤DC显著减少，血液DC明显降低。即使在移植后早期也检测到迁移性朗格汉斯细胞（LC）和真皮树突状细胞（DDC）的供体嵌合现象占主导，且其发展独立于化疗方案、移植物处理或移植后的时间点。在治疗开始前，患者外周血CD123+前DC2数量显著减少，而CD11c+前DC1数量似乎也减少，但与对照组在统计学上无显著差异。aHCT后宿主来源的pB前DC几乎不存在。在第56天左右细胞数量进一步减少后，两种前DC亚群均重建，并在第112天稳定至移植前数量。aGvHD的发生及其治疗使两种前DC亚群的数量均减少。此外，阿仑单抗预处理明显对两种前DC亚群的重建产生负面影响。
鉴于人类中GvHD的诱导与小鼠模型一样依赖宿主DC，研究不同部位尤其是GvHD靶器官中的DC嵌合现象和数量，可能为深入了解aHCT这一主要障碍的发病机制提供重要线索。
