Prolongation of cardiac allograft survival by selective injection of donorliver leukocytes in non-immunosuppressed rats

Liver grafts are spontaneously accepted in several animal combinations and are able to induce acceptance of another organ originating from the same do nor, which would be rejected when transplanted alone. However, the exact me chanism of this unique tolerance induction capability remains unclear. The aim of our study was to investigate the ability of nonparenchymal liver cel ls to induce tolerance when they were separated from their parenchymal envi ronment. In the murine combination we used (BN --> LEW), heart transplants were constantly tolerated after combined liver plus heart grafting, but rej ected when transplanted alone. Nonparenchymal liver cells were isolated fro m BN rat livers by enzymatic digestion and injected, at different times, to LEW rats, which were recipients of BN heart transplants. The average numbe r of mononuclear cells obtained after isolation was 20 x 10(6)/5 g of rat l iver. Immediate trypan-blue exclusion test showed more than 95% of viable c ells. Phenotypic studies showed a predominant (47%) lymphocyte population, 7% were monocytes and 46% were cellular debris. Among the lymphocyte popula tion, the majority of cells were bearing the NKR-P1 receptor and about 30% CD3 receptors. Inoculation of nonparenchymal liver cells 7 and 30 days prio r to heart transplantation significantly prolonged graft survival compared to controls (14.6 and 12.7 vs. 8.1 days; p = 0.0008 and 0.0059, respectivel y), whereas simultaneous injection (day 0) had no effect. Injection of dono r splenocytes or nonparenchymal liver cells from a third party, at any time , had no effect on rejection. These results provide some more evidence abou t the specific role of liver lymphocytes in allogenic unresponsiveness. The y also suggest that the hepatic parenchymal environment is necessary for th e optimal development of this phenomenon. Copyright (C) 2000 S. Karger AG,B asel.