Transgenic expression of protective molecules in porcine cells and tissues is a promising approach to prevent xenograft rejection. Viruses have developed various strategies to escape the host’s immune system. We generated porcine B cells (B cell line L23) expressing the human adenovirus protein E3/49K or the human cytomegalovirus protein pUL11 and investigated how human T, NK and B cell responses are affected by the expression of the viral proteins. Binding studies revealed that E3/49K and pUL11 interact with CD45 on human but not porcine peripheral blood mononuclear cells. T cell proliferation in response to L23-E3/49K cells was significantly reduced and accompanied by development of an anti-inflammatory cytokine milieu (low: TNF-alpha, IFN-gamma, IL-6; high: IL-4, IL-10). Human peripheral blood mononuclear cells which had been primed for four weeks by L23-E3/49K cells included an extended population of regulatory T cells. Cytotoxicity of effector T and natural killer cells against L23 cells was significantly reduced (40 to 50%) by E3/49K expression. B cell activation and antibody production to E3/49K expressing cells was also diminished. Surprisingly, pUL11 expression showed no effects. Reduction of human anti-pig immune responses by transgenic expression of selected viral genes may be a novel approach for protection of porcine xenografts.

在猪细胞和组织中转基因表达保护性分子是预防异种移植排斥的一种有前途的方法。病毒已经发展出各种策略来逃避宿主的免疫系统。我们生成了表达人腺病毒蛋白 E3/49K 或人巨细胞病毒蛋白 pUL11 的猪 B 细胞（B 细胞系 L23），并研究了病毒蛋白表达如何影响人 T、NK 和 B 细胞反应。结合研究表明，E3/49K 和 pUL11 与人类而非猪外周血单核细胞上的 CD45 相互作用。L23-E3/49K 细胞响应的 T 细胞增殖显着减少，并伴随抗炎细胞因子环境的发展（低：TNF-α、IFN-γ、IL-6；高：IL-4、IL-10） ）。已被 L23-E3/49K 细胞引发四周的人外周血单核细胞包括大量调节性 T 细胞。E3/49K 表达显着降低效应 T 细胞和自然杀伤细胞针对 L23 细胞的细胞毒性（40% 至 50%）。B 细胞活化和 E3/49K 表达细胞的抗体产生也减少。令人惊讶的是，pUL11 表达没有显示出任何影响。通过选定病毒基因的转基因表达来减少人抗猪免疫反应可能是保护猪异种移植物的新方法。