Department of Applied Biological Chemistry, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Cytotechnology. 2000 Jul;33(1-3):237-45. doi: 10.1023/A:1008102304740.
Although oral administration of a soluble proteinantigen can induce various immune responses, theeffect of the dosage of oral antigen on thepredominance of Th2-type cytokine and antibodyresponses has not been well clarified yet. In thepresent study, we fed T cell receptor (TCR) transgenic(tg) mice various amounts of chicken ovalbumin (0.1,5, and 250 mg) and examined the resulting immuneresponses to this antigen. In these TCR tg mice, theresponses of antigen-specific T cells were greatlyamplified concomitantly with significantantigen-specific cytokine secretion. We found that ahigh dose (250 mg) of antigen significantlyupregulated the serum antigen-specific IgG1 and IgAantibody responses in mice later intraperitoneallyinjected with antigen plus adjuvant. The miceadministered the same oral dose but not immunizedshowed upregulation of Th2-type IL-4 and IL-5secretion and downregulation of Th1-type IL-2 andIFN-gamma. This enhancement of Th2-type cytokineand antibody responses was more marked when largerdoses of antigen orally administered. These resultsdemonstrated that antigen feeding induces thedevelopment of T cells secreting Th2-type cytokines ina dose-dependent manner and that these T cells have ahelper function for the production of antibodies ofthe Th2-type isotypes. This experimental system shouldbe useful to screen foods and other substances thatcan modulate Th2-type responses relating to allergy.
虽然口服可溶性蛋白抗原可以诱导各种免疫反应，但口服抗原剂量对 Th2 型细胞因子和抗体反应优势的影响尚未得到很好的阐明。在本研究中，我们用鸡卵清蛋白（OVA；0.1、5 和 250mg）喂养 T 细胞受体（TCR）转基因（tg）小鼠，并检测了对该抗原的免疫反应。在这些 TCR tg 小鼠中，抗原特异性 T 细胞的反应与显著的抗原特异性细胞因子分泌一起大大扩增。我们发现，高剂量（250mg）的抗原显著上调了随后用抗原加佐剂腹腔内注射的小鼠血清中抗原特异性 IgG1 和 IgA 抗体反应。给予相同口服剂量但未免疫的小鼠表现出 Th2 型 IL-4 和 IL-5 分泌上调和 Th1 型 IL-2 和 IFN-γ下调。口服给予更大剂量的抗原时，Th2 型细胞因子和抗体反应的增强更为明显。这些结果表明，抗原喂养以剂量依赖性方式诱导分泌 Th2 型细胞因子的 T 细胞的发育，并且这些 T 细胞对 Th2 型同种型抗体的产生具有辅助功能。该实验系统应该有助于筛选可以调节与过敏相关的 Th2 型反应的食物和其他物质。
