Role of the liver in alloimmune response following inoculation of donor spleen cells

The liver is thought to be an immunologically privileged organ in the respo nse to inoculated antigens. We previously demonstrated that it is possible to localize inoculated antigens to the liver alone or only to extrahepatic tissue using orthotopic syngeneic liver transplantation (OSLT). In this stu dy, we analyzed more detailed mechanisms of the anti-alloimmune response in the liver. DA rat spleen cells were systemically injected into WS rats (do nor spleen cell inoculation, DSI). In the sensitized liver-grafted (SLG) gr oup, after DSI, liver grafts were retrieved from sensitized WS rats, then t ransplanted into naive WS rats. In the sensitized liver-removed (SLR) group , after DSI, WS rats were totally hepatectomized and given livers transplan ted from naive WS rats. All the rats were challenged with heterotopic heart grafts 10 days after DSI. Mean heart graft survival in the control, DSI, S LG, and SLR groups were 11.6 +/- 1.6, 10.7 +/- 2.4, 4.4 +/- 1.0, and 24.6 /- 6.3 days, respectively. Accelerated rejection in the SLG group as well a s graft prolongation in the SLR group disappeared when OSLT was performed 2 days after DSI or later. Irradiation of DA splenocytes before inoculation did not alter graft survival in SLG. However, pretreatment with gadolinium chloride prior to DSI attenuated the antidonor response in the SLG group. I n conclusion, a vigorous antidonor response occurred in the liver after sys temic inoculation of spleen cells. It peaked 1 day after DSI and disappeare d rapidly. Kupffer cells seemed to play an important role in this phenomeno n.