Gong Weihua, Liu Baoqing, Chen Juntao, Liu Chen, Shen Zhonghua
Department of Surgery, Second Affiliated Hospital of School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China (mainland).
Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA.
Ann Transplant. 2018 Apr 13;23:246-251. doi: 10.12659/AOT.907598.
BACKGROUND Although our previous studies revealed the role of Tregs (regulatory T cells) and MDSCs (myeloid-derived suppressor cells) in a pre-sensitized cardiac transplant model, interplay between Tregs and NK cells, neutrophils, and macrophages remain undefined. MATERIAL AND METHODS Mice heart transplantation with skin pre-sensitization was performed, in which prolonged-cold ischemia time (PCI) was used for donor treatment. Syngeneic heterotopic heart transplant recipients with PCI were treated with PC61 (monoclonal anti-CD25 antibodies), adoptive cell transfer with Tregs, and rapamycin. RESULTS We unveiled that both rapamycin treatment and adoptive transfer of Tregs could lead to a remarkable decrease of frequency of splenic Gr1+ cells (P=0.058 and P=0.016, respectively). Although administration of PC61 did not affect frequency of splenic Gr1+ cells, it dramatically increased frequency of splenic F4/80+ macrophages (P=0.052). Intriguingly, use of both exogenous PC61 and rapamycin induced a dramatic augmentation of frequency of Gr-1+ neutrophils in the grafts (PC61: P=0.00029; rapamycin: P=0.0096). Noticeably, all different regimens including PC61, rapamycin, and adoptive transfer of Tregs, consistently resulted in a remarked augmentation of frequency of F4/80+ macrophages within grafts (PC61, P=0.0013; rapamycin, P=0.015; Tregs transfer, P=0.013). Although rapamycin and adoptive transfer of Tregs did not affect frequency of NK1.1+ cells, administration of PC61 dramatically increased frequency of NK1.1+ cells within grafts (P=0.033). CONCLUSIONS Tregs depletion or Tregs induced by rapamycin or exogenous cell transfer could affect frequencies of both splenic and intragraft neutrophils, macrophages, and NK cells, but not splenic NK cells. Our data might shed light on understanding sensitized transplant biology.
尽管我们之前的研究揭示了调节性T细胞（Tregs）和髓源性抑制细胞（MDSCs）在预致敏心脏移植模型中的作用，但Tregs与自然杀伤细胞、中性粒细胞和巨噬细胞之间的相互作用仍不明确。材料与方法：进行皮肤预致敏的小鼠心脏移植，其中供体采用延长冷缺血时间（PCI）处理。对接受PCI的同基因异位心脏移植受体用PC61（抗CD25单克隆抗体）、Tregs过继性细胞转移和雷帕霉素进行治疗。结果：我们发现雷帕霉素治疗和Tregs过继性转移均可导致脾脏Gr1+细胞频率显著降低（分别为P = 0.058和P = 0.016）。尽管给予PC61不影响脾脏Gr1+细胞频率，但它显著增加了脾脏F4/80+巨噬细胞频率（P = 0.052）。有趣的是，同时使用外源性PC61和雷帕霉素可导致移植物中Gr-1+中性粒细胞频率显著增加（PC61：P = 0.00029；雷帕霉素：P = 0.0096）。值得注意的是，包括PC61、雷帕霉素和Tregs过继性转移在内的所有不同方案均一致导致移植物中F4/80+巨噬细胞频率显著增加（PC61，P = 0.0013；雷帕霉素，P = 0.015；Tregs转移，P = 0.013）。尽管雷帕霉素和Tregs过继性转移不影响NK1.1+细胞频率，但给予PC61显著增加了移植物中NK1.1+细胞频率（P = 0.033）。结论：Tregs耗竭或雷帕霉素诱导的Tregs或外源性细胞转移可影响脾脏和移植物内中性粒细胞、巨噬细胞和NK细胞的频率，但不影响脾脏NK细胞的频率。我们的数据可能有助于理解致敏移植生物学。
