Abstract
The liver has been demonstrated in many models to favor the induction of peripheral tolerance. The mechanisms mediating this phenomenon remain undefined. In this study, we delivered the C3H spleen cells (SCs) into the B6 liver through the portal vein (p.v.) in contrast to tail vein (i.v.) injection to characterize the liver leukocytes by flow cytometry and their function by MLR, ELISPOT, and immunohistochemistry assays. Heterotopic heart transplantation was performed from C3H donors to B6 recipients at day 7 post-treatment. The TCRαβ +NK1.1+ cells (NKT) were significantly increased in the liver, and CD4+CD25+Foxp3+ regulatory T cells (Treg) were markedly increased in the both liver and spleen after p.v. but not i.v. injection of C3H SCs. The proliferative activity of T cells from the p.v. treated mice was significantly suppressed and IL-2 was decreased, IL-4 and IL-10 were increased in vitro, suggesting that the role of the Treg may contribute to these responses. Further, significantly increased IL-4, IL-10, and IFN-γ production was detected from liver nonparenchymal cells under αGalCer stimulation, suggesting the role of liver NKT cells. Heart allograft survival was significantly prolonged in the C3H SCs p.v. treated recipients than in the i.v. treated recipients. Therefore, the liver can serve as a site of systemic tolerance induction. Both NKT cells and CD4+CD25+Foxp3+ Treg appear to be involved in the regulation of peripheral immune responses after antigen immunization of the liver.
