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首页> 外文期刊>Transplant immunology >Porcine cell microchimerism but lack of productive porcine endogenous retrovirus (PERV) infection in naive and humanized SCID-beige mice treated with porcine peripheral blood mononuclear cells.
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Porcine cell microchimerism but lack of productive porcine endogenous retrovirus (PERV) infection in naive and humanized SCID-beige mice treated with porcine peripheral blood mononuclear cells.

机译：猪细胞微嵌合体，但在用猪外周血单核细胞治疗的幼稚和人源化SCID-米色小鼠中缺乏生产性猪内源性逆转录病毒（PERV）感染。

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Pigs are considered a suitable source of cells and organs for xenotransplantation. All known strains of pigs contain porcine endogenous retrovirus (PERV) and PERV released by porcine cells may infect human cells in vitro and severe-combined immunodeficient (SCID) mice in vivo. Humanized SCID (hu-SCID) mice develop immune response to porcine antigens. Here we investigated PERV transmission in humanized SCID-beige mice using porcine peripheral blood mononuclear cells (PBMC) as the donor tissue (and the source of PERV). Mice were infused in the peritoneal cavity with 1.5-3.0 x 10(7) unfractionated human PBMC. Unfractionated porcine PBMC (1.5-3.0 x 10(7) cell/mouse) were infused to the mice simultaneously with human PBMC or 3 weeks after human PBMC infusion. The treated mice were monitored for weight and skin changes, donor cell chimerism, anti-pig antibodies and PERV transmission. All humanized mice tested 5-12 weeks after human PBMC transplantation were macrochimeric (up to 40% of cells in blood) for human cells, where 99% of the human cells were T-lymphocytes. Although human B lymphocytes were very rare in the blood of humanized mice at that point, the mice were positive for human anti-pig natural antibodies. The control SCID-beige mice or mice treated with porcine PBMC alone were negative for anti-porcine antibodies. Approximately 70% of the humanized mice treated with porcine PBMC were also microchimeric for porcine cells. Although some tissue samples of these mice were positive for PERV DNA in the absence of porcine DNA indicating PERV infection, the infection was non-productive as PERV transcripts were not detectable in those tissues. PERV infection of human and mouse cells in vitro by co-culturing with porcine PBMC was also non-productive. Humanized SCID-beige mice suffered weight loss and occasional minor skin changes due to graft vs. host disease caused by human PBMC but none of the mice showed observable effect attributable to the apparent PERV infection alone.
机译：猪被认为是异种移植的合适细胞和器官来源。所有已知的猪品系均含有猪内源性逆转录病毒（PERV），猪细胞释放的PERV可能会在体外感染人细胞，而在体内会感染严重合并免疫缺陷（SCID）小鼠。人源化SCID（hu-SCID）小鼠对猪抗原产生免疫应答。在这里，我们调查了猪外周血单核细胞（PBMC）作为供体组织（和PERV的来源）在人源化SCID-米色小鼠中的PERV传播。将1.5-3.0 x 10（7）普通人PBMC注入小鼠腹腔。将未分级的猪PBMC（1.5-3.0 x 10（7）细胞/小鼠）与人PBMC同时或在人PBMC输注后3周输注给小鼠。监测处理的小鼠的体重和皮肤变化，供体细胞嵌合体，抗猪抗体和PERV传播。在人PBMC移植后5至12周测试的所有人源化小鼠都是人细胞的大分子嵌合体（血液中多达40％的细胞），其中99％的人类细胞是T淋巴细胞。尽管那时人B淋巴细胞在人源化小鼠的血液中非常稀少，但这些小鼠对人抗猪天然抗体呈阳性。对照SCID-米色小鼠或仅用猪PBMC治疗的小鼠抗猪抗体阴性。约有70％的用猪PBMC治疗的人源化小鼠也是猪细胞的微嵌合体。尽管这些小鼠的一些组织样品在没有表明PERV感染的猪DNA的情况下对PERV DNA呈阳性，但由于在这些组织中无法检测到PERV转录本，因此这种感染是无效的。与猪PBMC共同培养对人和小鼠细胞的PERV感染也是无效的。由于人PBMC引起的移植物抗宿主病，人源化SCID-米色小鼠经历了体重减轻和偶尔的轻微皮肤变化，但没有一只小鼠表现出可观察到的效果，这仅归因于明显的PERV感染。

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