THE ROLE OF THE LIVER FOR THE INDUCTION OF ORAL TOLERANCE.

背景：我们试图分析肝脏作为调节器官在诱导口服免疫耐受中的作用。方法：采用口服卵清蛋白建立口服耐受模型进行分析。第一年：首先，我们利用同位素解离的抗原分析了口服抗原在体内的分布情况。其次，用免疫组织化学方法分析了肝组织巨噬细胞、树突状细胞、肝窦内皮细胞等抗原提呈细胞在口服耐受诱导过程中黏附分子或共刺激分子等功能分子的表达变化。&lt；第二年&gt；：我们用SAGE方法分析了口服耐受诱导过程中肝脏细胞因子表达的变化。通过对解离的活化T细胞的追逐，分析了经口耐受小鼠肝脏中活化T细胞进入肝脏后的存活情况。&lt；第三年&gt；：我们分析了哪种…更多的肝内调节细胞，如NKT或CD25/CD4阳性T细胞，通过阻断抗体参与口服耐受的诱导。我们还分析了诱导口服耐受小鼠肝脏中活化的T细胞凋亡的细胞机制。结果：第一年：我们明确了口服给药的抗原分布在肝脏。我们还发现，黏附分子或共刺激分子等功能分子在肝窦内皮细胞上表达上调，而在DC和巨噬细胞上均不表达。第二年：我们发现，与正常小鼠相比，口服耐受小鼠肝脏中细胞因子的表达谱没有明显的变化。另一方面，我们明确了活化的T细胞在进入口服耐受小鼠的肝脏后发生了凋亡。第三年：我们明确指出，没有一种单一的肝内免疫调节细胞，如NKT或CD25/CD4+T细胞参与口服耐受的诱导。另一方面，我们揭示了口服耐受小鼠肝脏中活化的T细胞的凋亡是由巨噬细胞引起的。结论：肝脏通过使肝脏中活化的T细胞发生凋亡而参与了口服耐受的诱导。较少

Background : We tried to analyze the role of the liver as the regulating-regulating organ for the induction of oral immunological tolerance.Methods : Oral tolerance model made by oral feeding of OVA was used for analyze. <First year> : At first we analyzed how the antigen administrated by orally distribute in the body by using isotope-raveled antigen. Second, we analyzed how the expression of functional molecules such as adhesion molecules or co-stimulating molecules on hepatic antigen presenting cells such as macrophage, dendritic cell or sinusoidal endothelial cell changed during the induction of oral tolerance by using immuno-histochemical method. <Second year> : We analyzed how the profile of cytokine expression in the liver changed during the induction of oral tolerance by using SAGE method. We also analyzed the situation of the life of activated T cell after entering the liver of oral tolerated mouse by chasing the raveled activated T cell. <Third year> : We analyzed what kind of … More intra hepatic regulatin-regulating cells such as NKT or CD25/CD4 positive T cell participated in the induction of oral tolerance by using blocking antibodies. We also analyzed the cellular mechanisms of the induction of apoptosis of activated T cell in the liver of oral tolerated mouse.Results : <First year> : We made clear that the antigen administrated by orally distribute to the liver. We also revealed that the expressions of functional molecules such as adhesion molecules or co-stimulating molecules were up regulated on hepatic sinusoidal endothelial cell but neither on DC nor macrophage. <Second year> : We revealed that there were no characteristic changes of the profile of cytokine expression in the liver of oral tolerated mouse compared with normal mouse. On the other hand we made clear that the activated T cell became to die by apoptosis after entering the liver of oral tolerated mouse. <Third year> : We made clear that no single kind of intra hepatic immune-regulating cells such as NKT or CD 25/CD4 positive T cell participate in the induction of oral tolerance. On the other hand we revealed that the apoptosis of activated T cell in the liver of oral tolerated mouse were caused by macrophage.Conclusion : These findings indicate that liver participates in the induction of oral tolerance by making the activated T cell apoptosis in the liver. Less