The immunosuppressive function of the α-fetoprotein

甲胎蛋白(α-FetoProtein，AFP)是一种在胎儿血清中含量较高的血清蛋白，在成人血清中不存在。然而，在肝细胞癌和卵黄囊肿瘤患者中，血清AFP经常升高。大量研究表明，免疫调节可能是AFP的生物学功能之一。为了阐明甲胎蛋白在体内的生物学功能，我们建立了一种在β-肌动蛋白启动子控制下携带人甲胎蛋白基因的转基因小鼠。在这只小鼠体内，可以观察到AFP的普遍表达。利用这些小鼠，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。我们已经证明，与野生鼠相比，AFP转基因鼠的所有这些实验性自身免疫性疾病的发展都受到了显著的抑制。在体外，转基因小鼠脾细胞的植物血凝素反应低于野生鼠。转基因小鼠的CD4+、CD8+胸腺细胞数量显著减少。这些观察表明，普遍产生的AFP调节体内T细胞的发育和/或T细胞依赖的免疫反应。目前，我们已经构建了AFP基因缺失小鼠的靶向表达载体。

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.