Nakamura T, Nakao T, Ashihara E, Yoshimura N
Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan.
Department of Organ Transplantation and General Surgery, Kyoto Prefectural University of Medicine, Kajii-cho 465, Kamigyo-ku, Kyoto-prefecture, Japan.
Transplant Proc. 2016 May;48(4):1275-8. doi: 10.1016/j.transproceed.2015.10.060.
Myeloid-derived suppressor cells (MDSCs) play an important role in regulating allograft rejection in organ transplantation. On the other hand, CD3(+)/CD4(+)/FOXP3(+) regulatory T cells (Tregs) also are of vital importance in immunological tolerance. We previously revealed that adoptive transfer of MDSCs recruited Tregs in the spleen. However, it is still uncertain whether MDSCs are capable of recruiting Tregs to an allograft in vivo.
We conducted adoptive transfer experiments of MDSCs to clarify the effects of MDSCs on Tregs in vivo.
Gr-1(+)/CD11b(+) MDSCs were isolated from rapamycin-treated cardiac transplant (CTx) recipients (3 mg/kg, intraperitoneally on postoperative days [POD] 0, 2, 4, and 6) on POD 7 by magnetic-activated cell sorting (purity >95%). In murine heterotopic cardiac transplantation, 2 × 10(6) MDSCs were transferred into the graft aorta 5 minutes before reperfusion.
Flow cytometric analyses of a cardiac allograft on POD 7 showed that MDSCs derived from rapamycin-treated CTx mice (MDSCs-Rap) transfer led to significant recruitment of Tregs compared with a PBS-injected allograft. The level of programmed death ligand-1 (PD-L1) on MDSCs-Rap was higher than those from non-treated recipients. Furthermore, pathological findings also confirmed accumulation of Foxp3(+) Tregs in an allograft.
Induced PD-L1 on MDSCs might result in recruitment of Tregs. These results suggested that functional MDSCs possessed an ability to induce Tregs in a cardiac allograft and developed a tendency to immunological tolerance.
髓源性抑制细胞（MDSCs）在调节器官移植中的同种异体移植排斥反应中起重要作用。另一方面，CD3(+)/CD4(+)/FOXP3(+)调节性T细胞（Tregs）在免疫耐受中也至关重要。我们之前发现，过继转移MDSCs可在脾脏中募集Tregs。然而，MDSCs在体内是否能够将Tregs募集至同种异体移植物仍不确定。
我们进行了MDSCs的过继转移实验，以阐明MDSCs在体内对Tregs的影响。
在术后第7天，通过磁珠分选法（纯度>95%）从接受雷帕霉素治疗的心脏移植（CTx）受者（术后第0、2、4和6天腹腔注射3mg/kg）中分离出Gr-1(+)/CD11b(+) MDSCs。在小鼠异位心脏移植中，在再灌注前5分钟将2×10(6)个MDSCs注入移植心脏的主动脉。
对术后第7天的心脏同种异体移植物进行流式细胞术分析显示，与注射PBS的同种异体移植物相比，来自雷帕霉素治疗的CTx小鼠的MDSCs（MDSCs-Rap）转移导致Tregs的显著募集。MDSCs-Rap上的程序性死亡配体-1（PD-L1）水平高于未治疗受者的MDSCs。此外, 病理结果也证实了同种异体移植物中Foxp3(+) Tregs的积聚。
MDSCs上诱导产生的PD-L1可能导致Tregs的募集。这些结果表明，功能性MDSCs具有在心脏同种异体移植物中诱导Tregs的能力，并形成免疫耐受倾向。
