Inoue Seiichiro, Tahara Kazunori, Kaneko Takashi, Ajiki Takashi, Takeda Shinichi, Sato Yuki, Hakamata Yoji, Murakami Takashi, Takahashi Masafumi, Kaneko Michio, Kobayashi Eiji
Division of Organ Replacement Research, Center for Molecular Medicine, Jichi Medical School, 3311-1, Yakushiji, Minamikawachi, Kawachi, Tochigi 329-0498, Japan.
Transpl Immunol. 2004 Jan;12(2):123-31. doi: 10.1016/j.trim.2003.10.001.
Donor passenger leukocytes (DPLs) that migrate after organ transplantation stimulate the recipient immune system and normally cause rejection and graft vs. host reaction. However, DPLs also contribute to the unresponsiveness to the donor organ. The quantity and quality of these migrating cells are considered dependent on individual transplanted organs. We compared the DPLs of the liver, which might contain somatic stem cells, with those of intestinal grafts that have highly immunogenetic cells. To study DPLs over a long period, we used green fluorescent protein (GFP) transgenic (Tg) rats developed by us as donors.
We performed orthotopic liver transplantation (OLT) and small bowel transplantation (SBT) from GFP Tg rats to wild recipients. A short course of tacrolimus (0.64 mg/kg, intramuscularly) was used to prevent antigenicity of the GFP. The fate of the DPLs in the peripheral blood and the recipient bone marrow was monitored by flow cytometry. Using long-surviving recipients, the GFP(+) cells in the graft and various host immunologic organs were measured and characterized by immunohistochemical staining.
In both groups, the numbers of the GFP(+) cells in the peripheral blood increased transiently and then gradually decreased to undetectable levels. While no GFP(+) cells were identified in the long-surviving-recipient bone marrow, there were a few GFP(+) cells in the graft liver, graft mesenteric lymph nodes and the recipient spleen. These cells showed major histocompatibility complex (MHC) class II antigen. There was no significant difference in the migration patterns of the GFP(+) cells in the OLT and SBT rats.
In both the OLT and SBT groups, the DPLs migrated transiently in the recipient peripheral blood. A small numbers of MHC class II-positive DPLs were present at the graft site and in the host spleen, but not in the bone marrow. There were no significant differences in the migration patterns of the DPLs between the OLT and SBT rats over the long term.
器官移植后迁移的供体乘客白细胞（DPLs）会刺激受体免疫系统，通常会引发排斥反应和移植物抗宿主反应。然而，DPLs也会导致对供体器官的无反应性。这些迁移细胞的数量和质量被认为取决于个体移植器官。我们将可能含有体细胞干细胞的肝脏的DPLs与具有高免疫原性细胞的肠道移植物的DPLs进行了比较。为了长期研究DPLs，我们使用我们培育的绿色荧光蛋白（GFP）转基因（Tg）大鼠作为供体。
我们从GFP Tg大鼠向野生受体进行了原位肝移植（OLT）和小肠移植（SBT）。使用短疗程的他克莫司（0.64mg/kg，肌肉注射）来防止GFP的抗原性。通过流式细胞术监测外周血和受体骨髓中DPLs的命运。利用长期存活的受体，通过免疫组织化学染色测量并表征移植物和各种宿主免疫器官中的GFP(+)细胞。
在两组中，外周血中GFP(+)细胞的数量短暂增加，然后逐渐减少至检测不到的水平。虽然在长期存活受体的骨髓中未发现GFP(+)细胞，但在移植肝脏、移植肠系膜淋巴结和受体脾脏中有少量GFP(+)细胞。这些细胞显示出主要组织相容性复合体（MHC）II类抗原。OLT和SBT大鼠中GFP(+)细胞的迁移模式没有显著差异。
在OLT和SBT组中，DPLs均在受体外周血中短暂迁移。少量MHC II类阳性DPLs存在于移植部位和宿主脾脏中，但不存在于骨髓中。长期来看，OLT和SBT大鼠中DPLs的迁移模式没有显著差异。
