Participation of the liver in generation of a vigorous anti-donor responseafter inoculation of donor spleen cells

Background. There is a general agreement that a preferential accumulation o f alloantigens within the Liver could induce hyporesponsiveness to the inoc ulated antigens. Entrapment of antigens in the Liver may evoke an unique im mune response in the organ and play a key role in determination of the fate of the transplanted grafts. To understand the immune response in the liver after inoculation of allogeneic donor antigens, we examined the immune res ponse to systemically inoculated alloantigen in rats whose sensitized liver was replaced with that of naive rats or in naive rats whose liver was repl aced with that of sensitized rats. Methods. Using implantation of syngeneic liver (alloantigen-accumulated/nai ve) in rats (naive/alloantigen-sensitized), we compared the immune response s to alloantigen between rats with hepatic/extrahepatic alloantigen at 24 h r after alloantigen inoculation. This was called sensitized-liver-grafted ( SLG)/sensitized-liver-removed (SLR) treatment. The immune response to donor alloantigen in this model was evaluated by survival of skin or heart graft s, complement-dependent cytotoxicity (CDC) titer and delayed-type hypersens itivity (DTH) response. Results. Compared with the mean survival time (MST) in donor spleen cell in oculated (DSI) rats (skin and heart, MST: 8.2+/-1.1 and 10.7+/-2.3 days), S LG rats rejected allografts in an accelerated fashion (skin and heart, MST: 5.5+/-0.5 and 4.2+/-0.8 days), associated with higher CDC titer and DTH re sponse. In contrast, allograft survival was moderately prolonged in SLR (sk in and heart, MST: 16.5+/-2.6 and 29.5+/-3.7 days)associated with suppresse d CDC titer and DTH response. The survival of third-party allograft after S LG or SLR treatment (skin, MST: 9.3+/-1.5 or 9.7+/-0.6 days) indicated that immunological hyper/hyporesponsiveness was donor-specific. Conclusions. A strong anti donor immune response was induced by the transfe r of donor antigen-baring Liver to naive rats 24 hr after alloantigen inocu lation, whereas removal of the liver suppressed alloimmune response. Our re sults indicate that vigorous anti-alloimmune response occurred in the liver after systemic inoculation of donor spleen cells.