The immunosuppressive function of the α-fetoprotein

甲胎蛋白（AFP）是一种血清蛋白，在胎儿血清中含量可观，但在成人血清中含量不高。然而，血清甲胎蛋白经常升高，肝细胞癌和卵黄囊肿瘤患者。大量研究表明，免疫调节可能是AFP的生物学功能之一。为了阐明AFP在体内的生物学功能，我们建立了一种转基因小鼠，它具有β-actin启动子控制的人AFP基因。在该小鼠中，观察到AFP的普遍表达。使用这些小鼠，我们已经分析了实验性自身免疫性疾病，如关节炎，自身免疫性甲状腺炎和实验性脑脊髓炎。我们已经表明，与野生小鼠相比，所有这些实验性自身免疫性疾病的发展在AFP产生的转基因小鼠中被显着抑制。转基因小鼠脾细胞的体外植物血凝素反应低于野生型小鼠。转基因小鼠胸腺内CD 4+、CD 8+细胞数明显减少。这些观察结果表明，普遍产生的AFP调节体内T细胞发育和/或T细胞依赖性免疫应答。目前，我们已经构建了AFP基因敲除小鼠的靶向质粒。

α-fetoprotein (AFP) is a serum protein in appreciable amounts in fetal but not in adult serum. However, serum AFP is frequently elevated in patients with hepatocellular carcinomas and yolk sac tumors. Numerous studies have suggested that immunomodulation may be one of the biological functions of AFP. To clarify the biological function of the AFP in vivo, we have established a transgenic mouse, which has a human AFP gene under the control of β-actin promoter. In this mouse, ubiquitous expression of AFP is observed. Using these mice, we have been analyzed experimental autoimmune diseases, such as arthritis, autoimmune thyroiditis and experimental encephalomyelitis. We have showed that development of all these experimental autoimmune diseases were significantly suppressed in AFP produced transgenic mice compared with wild mice. In vitro phytohemagglutinin response of splenocytes from transgenic mice was lower than that from wild mice. Significantly reduced numbers of CD4+, CD8+ thymocytes were found in the transgenic mice. These observations suggest that ubiquitously produced AFP modulate in vivo T cell development and/or T cell dependent immune responses. Now, we have constructed the targeting plasmid for establishment of the AFP gene disrupted mice.