The effects of perioperative portal venous inoculation with donor lymphocytes on allograft survival in the rat.

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Effects of perioperative portal venous inoculation of donor lymphocytes on renal allograft survival were tested in rat system. Untreated Lewis hosts rejected BN renal grafts at 7.8+0.6 days. IV administration of 1x10 BN cells to LEW hosts on day 0 caused a slight, but not significant prolongation of renal graft survival(MST=9.5+3.0 days), whereas PV inoculation of 1x10 BN cells on day 0 remarkably prolonged renal graft survival to 22.2+5.3 days(p 0.01). The prolongation of the graft survival was antigen-specific. When serum from PV-treated LEW hosts was added to MLC at a concentration of 3% of total volume, it suppressed the MLC reaction toward BN cells by 71%, but not toward third-party DA stimulators. Adoptive transfer of the serum into the virgin secondary LEW hosts significantly prolonged the graft survival of BN kidney from 7.8 to 18.9+5.5 days, but not third-party DA graft survivals(MST=7.5+0.6 days). The amounts of in vitro cytokine production of graft-infiltrating-cells(GIC) from tolerant hosts after mitogen stimulation were remarkably decreased(IL-2:8.7+1.4 U/ml, IL-3:15.4+0.6U/ml, and IL-6:24.6+3.5 U/ml) than those of uninoculated control hosts during ongoing rejection(IL-2:19.6+2.9 U/ml, IL-3:22.2+2.7 U/ml, and IL-6:67.5+13.2U/ml). The percentage of cytotoxic/suppressor T cells(OX-8) and Ia-positive cells(OX-6) in GIC cells(23.1+4.4% and 9.0+2.0%, respectively) from PV inoculated LEW hosts on day 6 postgrafting were significantly lower than those of uninoculated control recipients(39.4+8.2% and 23.0+1.9%, respectively). Cytolytic activity of GIC from tolerant hosts toward donor blastoid lymphocytes was significantly decreased(19.0+1.2%), compared with that from control allografts during ongoing rejection(51.5+5.3%). These results demonstrated that activation of both Th and Tc cells was inhibited in situ in renal allograft following administration of donor lymphocytes through the portal vein.