Induction of immune hyporesponsiveness after portal vein immunization withovalbumin

Background. Previous work has demonstrated Prolonged allograft survival aft er donor-specific portal vein immunization before the transplantation. The purpose of this study was to examine the potential mechanism of portal vein -induced hyporesponsiveness after portal vein immunization with the soluble protein ovalbumin. Methods. Balb/c mire were immunized with a portal vein injection of ovalbumin. After the immunization, in vivo delayed-type hypers ensitivity response and in vitro proliferative response of ovalbumin-specif ic T cells were assessed to determine host immune response. Type 1 (IL-2, I L-12, IFN-gamma) and type 2 (IL-4, TCF-beta) regulatory cytokines were asse ssed by semiquantitative reverse transcriptase polymerase chain reaction. S era anti-ovalbumin Igc, IgG1, and IgG2a were measured by enzyme-linked immu nosorbent assay, and the antigen-presenting ability of liver nonparenchymal cells (NPCs) was assessed by T-cell proliferation to ovalbumin in vitro. R esults. There was significant inhibition of ovalbumin-specific delayed-type hypersensitivity and T-cell proliferation in portal vein-immunized mice co mpared with intraperitoneal-immunized or control mice. Reverse transcriptas e polymerase chain reaction analysis results showed that lymphocytes from p ortal vein-immunized mice exhibited decreased type I and increased type 2 c ytokine messenger RNA expression compared with intraperitoneal-immunized or control animals. The type 2 cytokine response of lymphocytes from ovalbumi n portal vein-immunized mice correlated with increased sera or,ovalbumin-Ig G1 and decreased IgG2a. The results of an antigen-presenting assay revealed that liver NPCs were deficient antigen-presenting cells compared with adhe rent cells from heart or spleen. Conclusions. Processing of ovalbumin by he patic NPCs results in hyporesponsiveness to ovalbumin by an impaired type I cytokine response and a preferential shift toward a type 2 cytokine respon se, possibly because of defective antigen presentation by hepatic NPCs. Int rahepatic processing of antigen may play an important role in the developme nt of strategies to reduce host immunoreactivity against transplanted allog rafts.