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.
Li
Wei
W
Division of Transplantation, Department of Surgery, University of Washington Medical Center, Seattle, WA, USA.
Chou
Sonja T
ST
Wang
Celso
C
Kuhr
Christian S
CS
Perkins
James D
JD
D000284:Administration, Oral; D000818:Animals; D000941:Antigens / Q000008:administration & dosage / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D007376:Interleukin-2 / Q000378:metabolism; D015847:Interleukin-4 / Q000378:metabolism; D008099:Liver / Q000276:immunology* / Q000378:metabolism / Q000601:surgery; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D010047:Ovalbumin / Q000008:administration & dosage / Q000276:immunology; D013154:Spleen / Q000276:immunology / Q000378:metabolism
D000941:Antigens; D007376:Interleukin-2; D015847:Interleukin-4; D010047:Ovalbumin