Li Jiatao, Li Xisheng, Liang Cai, Ling Lijun, Chen Zhiwei, Wong Chun Kwok, Waldmann Herman, Lui Kathy O
Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Li Ka Shing Institute of Health Sciences, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Department of Chemical Pathology, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
Biomaterials. 2020 Jul;248:120013. doi: 10.1016/j.biomaterials.2020.120013. Epub 2020 Apr 2.
We have previously demonstrated that short-term coreceptor blockade with non-lytic monoclonal antibodies enables the long-term survival of fully allogeneic embryonic stem cell (ESC) transplants in mice. Here, we describe the use of Hu-PBL humanized mice to determine whether short-term coreceptor blockade with humanized anti-human CD4 and CD8 antibodies can achieve the same outcome towards human ESC derivatives. While control Hu-PBL mice rejected allogeneic hESC-derived transplants within weeks, mice treated with coreceptor blocking antibodies held their grafts for 7 weeks, the duration of the study. Rejection in the control mice was associated with demonstrable infiltrates of human CD45 white blood cells, predominantly of CD8 T-cells, whereas anti-CD4, but not anti-CD8 antibody treated mice showed remarkably reduced lymphocyte infiltration and prolonged allograft survival, indicating that the CD4 T-cells were crucial to the rejection process. Our results give support to the principle that short-term blockade of T-cell co-receptors can achieve long-term acceptance of regenerative cell transplants in humans.
我们之前已经证明，使用非溶细胞性单克隆抗体进行短期共受体阻断能够使完全异基因的胚胎干细胞（ESC）移植在小鼠体内长期存活。在此，我们描述了使用人源化外周血淋巴细胞（Hu-PBL）小鼠来确定用抗人CD4和CD8人源化抗体进行短期共受体阻断是否能对人ESC衍生物产生相同的结果。虽然对照Hu-PBL小鼠在数周内排斥异基因hESC衍生的移植，但用共受体阻断抗体治疗的小鼠在长达7周的研究期间内维持了其移植。对照小鼠中的排斥反应与可证实的人CD45白细胞浸润有关，主要是CD8 T细胞，而抗CD4但非抗CD8抗体治疗的小鼠显示淋巴细胞浸润显著减少且同种异体移植存活期延长，表明CD4 T细胞对排斥过程至关重要。我们的结果支持了T细胞共受体短期阻断能够实现人类再生细胞移植长期接受的原则。
