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

• Project/Area Number: 13670564
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Jikei University School of Medicine
• Principal Investigator: TAKAHASHI Hiroki Jikei University School of Medicine, Lecturer, 医学部, 講師 (80256403)
• Co-Investigator(Kenkyū-buntansha): ZENIYA Mikio Jikei University School of Medicine, Assistant Professor, 医学部, 助教授 (70138767) ; TODA Gotaro Jikei University School of Medicine, Professor, 医学部, 教授 (40090500)
• Project Period (FY): 2001 – 2003
• Project Status: Completed (Fiscal Year 2003)
• Budget Amount: ¥3,500,000 (Direct Cost: ¥3,500,000); Fiscal Year 2003: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2002: ¥1,100,000 (Direct Cost: ¥1,100,000); Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
• Keywords: ORAL TOLERANCE / LIVER / REGURATORY CELL / 経口寛容誘導 / 肝内免疫環境 / 活性化リンパ球 / アポトーシス / IL-10・IL-12 / 肝内類洞内皮細胞 / 肝内樹状細胞

Research Abstract

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 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.