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

背景资料：方法：采用口服卵清蛋白（OVA）建立小鼠口服免疫耐受模型，分析肝脏在诱导小鼠口服免疫耐受中的调控作用。<First year>本文首先用同位素示踪法分析了口服抗原在体内的分布情况。第二，采用免疫组化方法分析了口服免疫耐受诱导过程中肝脏抗原呈递细胞如巨噬细胞、树突状细胞和肝窦内皮细胞表面粘附分子和共刺激分子表达的变化。<Second year>采用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。并通过追踪脱落的活化T细胞，分析活化T细胞进入口服耐受小鼠肝脏后的存活情况。<Third year>：我们分析了什么样的 ...更多信息 肝内调节细胞如NKT或CD 25/CD 4阳性T细胞参与阻断抗体诱导的口服耐受。结果：经口给予抗原后，小鼠肝脏中活化的T细胞发生凋亡，而经口给予抗原后，小鼠肝脏中活化的T细胞发生凋亡，而经口给予抗原后，小鼠肝脏中活化的T细胞<First year>发生凋亡。肝窦内皮细胞上粘附分子、共刺激分子等功能分子的表达上调，而DC和巨噬细胞上均未上调。<Second year>:结果表明，与正常小鼠相比，口服耐受小鼠肝脏细胞因子表达谱无特征性变化。另一方面，我们明确了活化的T细胞进入口服耐受小鼠的肝脏后，通过凋亡而死亡。<Third year>:表明肝内免疫调节细胞如NKT或CD 25/CD 4阳性T细胞均不参与口服免疫耐受的诱导。结论：肝脏通过诱导肝脏活化T细胞凋亡参与了口服耐受的诱导。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