Role of the Liver in Peripheral Tolerance: Induction Through Oral Antigen Feeding

Using a murine liver transplant model, we studied the liver's role in peripheral tolerance. Livers from BALB/c mice fed with ovalbumin (OVA) at either a low or high dose were transplanted into syngeneic recipients. Non-fed recipients were controls. Orthotopic liver transplantation (OLTx) was followed by OVA immunization and delayed-type hypersensitivity (DTH) challenge. The ex vivo adoptive transfer effect of liver nonparenchymal cells (NPCs) or spleen cells (SCs) from OVA-fed mice was examined. In vitro proliferative assays and cytokine profiles were conducted on NPCs and SCs from transplant recipients. Livers from all OVA-fed mice after 10 days transferred tolerance to OVA-naïve mice. The time course of adoptive transfer of liver NPCs from high-dose OVA-fed mice transferred OVA tolerance within 24 h; low-dose OVA-fed mice required > or = 4 days to transfer tolerance. The in vitro proliferative response of the NPCs to OVA revealed a decreased response in both dosage groups over the control group. Our results suggest that the liver plays an important role in inducing peripheral tolerance in a mucosal tolerance model, especially feeding high-dose OVA.