RESTORATION OF TOLERANCE TO RAT HEPATIC ALLOGRAFTS BY SPLEEN-DERIVED PASSENGER LEUKOCYTES

The tolerance induced by orthotopic liver transplantation (OLT) in cer tain combinations of rat strains can be prevented by total body irradi ation (TBI) of the donor. We demonstrate here that the intravenous ino culation of splenic leukocytes into irradiated donors before OLT could re-establish tolerance in association with a state of microchimerism detected in the recipients. When donor DA (RT1(a)) strain rats were ir radiated with 1000 rad 24 h before liver harvesting and subsequent liv er implantation into PVG recipients, five out of six rats died from re jection in this normally tolerogenic OLT (DA-PVG) combination. Injecti on of 1.5 x 10(8) splenic leukocytes from naive DA rats into the irrad iated DA donor rats 24 h before OLT restored the tolerogenic potential of the liver allografts. Immunofluorescence assay revealed an increas ed number of donor (DA) type cells in the PVG recipient bearing a repo pulated DA liver, compared to the PVG recipient of an irradiated liver , These results suggest that passenger leukocytes reconstituted by spl enic leukocytes have the capacity to protect liver allografts.