Saiki T, Ezaki T, Ogawa M, Matsuno K
Department of Anatomy I, Dokkyo University School of Medicine, 880 Kitakobayashi, Mibu, Tochigi 321-0293, Japan.
Transplantation. 2001 Jun 27;71(12):1806-15. doi: 10.1097/00007890-200106270-00017.
Kinetics and role of host and donor dendritic cells (DCs) in transplantation immunity are still ill-defined. Using a rat cardiac transplantation model, we studied DC trafficking and sites for allosensitization.
Host and donor DCs were defined as host- or donor-type class II major histocompatibility complex antigen single-positive cells by double-immunostaining. Proliferative response of both donor and host cells were also analyzed.
Host DCs were recruited to the graft soon after transplantation. These cells represented definitive precursors because of high labeling index by a continuous bromodeoxyuridine infusion, their small round shape, and their putative bone marrow origin. Donor interstitial DCs showed a significant self-replicating capability. Both recruited host DCs in a regraft experiment and donor DCs preferentially performed blood-borne migration to the T-cell area of host spleen. Furthermore, they also migrated to the T-cell area of hepatic lymph nodes after executing the sinusoids-lymph translocation as a novel pathway for these DCs. Selectively at their migration sites, a strong T-cell proliferative response occurred, which preceded that in the graft tissues. Removal of spleen and hepatic lymph nodes significantly prolonged the mean graft survival time.
We conclude that allogeneic heart transplantation induces the recruitment of host DC precursors to the graft tissues and the blood-borne migration of both recruited host and donor DCs to the host spleen and hepatic nodes where effector cells are predominantly sensitized.
宿主和供体树突状细胞(DCs)在移植免疫中的动力学及作用仍不明确。我们利用大鼠心脏移植模型研究了DC的迁移及同种致敏位点。
通过双重免疫染色将宿主和供体DC定义为宿主型或供体型II类主要组织相容性复合体抗原单阳性细胞。同时分析了供体细胞和宿主细胞的增殖反应。
移植后不久,宿主DC即被募集至移植物。这些细胞具有明确的前体细胞特征,因为持续注入溴脱氧尿苷后其标记指数高、呈小圆形且推测起源于骨髓。供体间质DC显示出显著的自我复制能力。在再次移植实验中,募集的宿主DC和供体DC均优先通过血行迁移至宿主脾脏的T细胞区。此外,它们在经窦状隙-淋巴转运这一新型DC迁移途径后,还迁移至肝淋巴结的T细胞区。在其迁移位点选择性地出现了强烈的T细胞增殖反应,且早于移植物组织中的反应。切除脾脏和肝淋巴结可显著延长移植物平均存活时间。
我们得出结论,同种异体心脏移植可诱导宿主DC前体细胞募集至移植物组织,并使募集的宿主和供体DC通过血行迁移至宿主脾脏和肝淋巴结,而效应细胞主要在此处被致敏。