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.

中文翻译：

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靶向CD4和CD8的共受体阻断可以在人源化小鼠中接受同种异体人多能干细胞移植。

我们以前已经证明，使用非溶解性单克隆抗体进行的短期共受体阻断可以在小鼠中实现完全同种异体胚胎干细胞（ESC）移植的长期存活。在这里，我们描述了使用Hu-PBL人源化小鼠来确定是否可以用人源化抗人CD4和CD8抗体进行短期共受体阻断，从而可以达到针对人ESC衍生物的相同结果。虽然对照Hu-PBL小鼠在数周内拒绝了同种异体hESC来源的移植，但接受共受体阻断抗体治疗的小鼠将其移植物保留了7周，即研究持续时间。对照小鼠的排斥反应与可证实的人类CD45白细胞浸润有关，主要是CD8 T细胞，而抗CD4，但未使用抗CD8抗体治疗的小鼠却表现出明显的淋巴细胞浸润减少和同种异体移植生存期延长，表明CD4 + T细胞对于排斥过程至关重要。我们的研究结果支持以下原则：短期阻断T细胞共受体可以使人类长期接受再生细胞移植。